PMID- 36068374 OWN - NLM STAT- MEDLINE DCOM- 20230123 LR - 20230123 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 482 IP - 1 DP - 2023 Jan TI - Updates on eosinophilic disorders. PG - 85-97 LID - 10.1007/s00428-022-03402-8 [doi] AB - This review addresses changes and updates in eosinophilic disorders under the International Consensus Classification (ICC). The previous category of myeloid/lymphoid neoplasm with eosinophilia (M/LN-eo) and a specific gene rearrangement is changed to M/LN-eo with tyrosine kinase gene fusions to reflect the underlying genetic lesions. Two new members, M/LN-eo with ETV6::ABL1 fusion and M/LN-eo with various FLT3 fusions, have been added to the category; and M/LN-eo with PCM1::JAK2 and its genetic variants ETV6::JAK2 and BCR::JAK2 are recognized as a formal entity from their former provisional status. The updated understanding of the clinical and molecular genetic features of PDGFRA, PDGFRB and FGFR1 neoplasms is summarized. Clear guidance as to how to distinguish these fusion gene-associated disorders from the overlapping entities of Ph-like B-acute lymphoblastic leukemia (ALL), de novo T-ALL, and systemic mastocytosis is provided. Bone marrow morphology now constitutes one of the diagnostic criteria of chronic eosinophilic leukemia, NOS (CEL, NOS), and idiopathic hypereosinophilia/hypereosinophilic syndrome (HE/HES), facilitating the separation of a true myeloid neoplasm with characteristic eosinophilic proliferation from those of unknown etiology and not attributable to a myeloid neoplasm. CI - © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Tzankov, Alexandar AU - Tzankov A AD - Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. FAU - Reichard, Kaaren K AU - Reichard KK AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, NY, Rochester, USA. FAU - Hasserjian, Robert P AU - Hasserjian RP AD - Department of Pathology, Massachusetts General Hospital, MA, Boston, USA. FAU - Arber, Daniel A AU - Arber DA AD - Department of Pathology, University of Chicago, IL, Chicago, USA. FAU - Orazi, Attilio AU - Orazi A AD - Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX, USA. FAU - Wang, Sa A AU - Wang SA AUID- ORCID: 0000-0001-9385-9911 AD - Department of Hematopathology, Division of Pathology, The University of Texas MD Anderson Cancer Center, TX, Houston, USA. Swang5@mdanderson.org. LA - eng PT - Journal Article PT - Review DEP - 20220907 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta) RN - 0 (Oncogene Proteins, Fusion) SB - IM MH - Humans MH - *Hypereosinophilic Syndrome/diagnosis/genetics MH - *Leukemia/pathology MH - *Myeloproliferative Disorders/diagnosis/genetics/pathology MH - Receptor, Platelet-Derived Growth Factor beta/genetics MH - Bone Marrow/pathology MH - Oncogene Proteins, Fusion/genetics OTO - NOTNLM OT - Chronic eosinophilic leukemia OT - ETV6::ABL1; FLT3 rearrangement OT - Idiopathic hypereosinophilic syndrome OT - Myeloid/lymphoid neoplasm with eosinophilia OT - NOS OT - Tyrosine kinase gene fusion EDAT- 2022/09/07 06:00 MHDA- 2023/01/24 06:00 CRDT- 2022/09/06 23:29 PHST- 2022/07/26 00:00 [received] PHST- 2022/08/23 00:00 [accepted] PHST- 2022/08/15 00:00 [revised] PHST- 2022/09/07 06:00 [pubmed] PHST- 2023/01/24 06:00 [medline] PHST- 2022/09/06 23:29 [entrez] AID - 10.1007/s00428-022-03402-8 [pii] AID - 10.1007/s00428-022-03402-8 [doi] PST - ppublish SO - Virchows Arch. 2023 Jan;482(1):85-97. doi: 10.1007/s00428-022-03402-8. Epub 2022 Sep 7. PMID- 36651066 OWN - NLM STAT- MEDLINE DCOM- 20230120 LR - 20230120 IS - 1699-3993 (Print) IS - 1699-3993 (Linking) VI - 58 IP - 12 DP - 2022 Dec TI - Pacritinib for myelofibrosis in adults with thrombocytopenia. PG - 577-589 LID - 10.1358/dot.2022.58.12.3474538 [doi] AB - Myelofibrosis is a rare progressive cancer of the bone marrow that disrupts the normal production of healthy blood cells, leading to bone marrow failure. Patients with myelofibrosis and severe thrombocytopenia (platelet count below 50 × 10(9)/L) have a wide range of unmet medical needs compared with those without thrombocytopenia. Usually, these patients have an increased disease burden, increased transfusion dependence, shorter overall survival, and limited treatment options. Pacritinib is a new oral kinase inhibitor specifically targeting Janus kinase 2 (JAK2), interleukin-1 receptor-associated kinase 1 (IRAK-1) and colony-stimulating factor 1 receptor (CSF-1R), and is indicated for the treatment of adults with moderate or high risk of primary or secondary myelofibrosis (post-polycythemia or post-primary thrombocytopenia) whose platelet count is less than 50 × 10(9)/L. In this review, we introduce pacritinib and make a brief comparison of different JAK inhibitors in clinical application. CI - Copyright 2022 Clarivate. FAU - Yang, Dong-Hua AU - Yang DH AD - Department of Pharmaceutical Sciences, St. John's University, Queens, New York City, New York, USA. yangd1@stjohns.edu. FAU - Lu, Qisi AU - Lu Q AD - Foresea Life Insurance Guangzhou General Hospital, Guangzhou, China. FAU - Zhu, Zhaohui AU - Zhu Z AD - Foresea Life Insurance Guangzhou General Hospital, Guangzhou, China. FAU - Huang, Guanghao AU - Huang G AD - Foresea Life Insurance Guangzhou General Hospital, Guangzhou, China. FAU - Young, Katherine AU - Young K AD - Department of Pharmaceutical Sciences, St. John's University, Queens, New York City, New York, USA. LA - eng PT - Journal Article PT - Review PL - Spain TA - Drugs Today (Barc) JT - Drugs of today (Barcelona, Spain : 1998) JID - 101160518 RN - 0 (11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene) RN - 0 (Bridged-Ring Compounds) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) SB - IM MH - Adult MH - Humans MH - Bridged-Ring Compounds/therapeutic use MH - *Primary Myelofibrosis/drug therapy MH - *Protein Kinase Inhibitors/therapeutic use MH - Pyrimidines/therapeutic use MH - *Thrombocytopenia/drug therapy OTO - NOTNLM OT - Fms-like tyrosine kinase 3 (FLT3) inhibitors OT - Janus kinase 2 (JAK2) inhibitors OT - Myelofibrosis OT - Pacritinib OT - Thrombocytopenia EDAT- 2023/01/19 06:00 MHDA- 2023/01/20 06:00 CRDT- 2023/01/18 03:23 PHST- 2023/01/18 03:23 [entrez] PHST- 2023/01/19 06:00 [pubmed] PHST- 2023/01/20 06:00 [medline] AID - 3474538 [pii] AID - 10.1358/dot.2022.58.12.3474538 [doi] PST - ppublish SO - Drugs Today (Barc). 2022 Dec;58(12):577-589. doi: 10.1358/dot.2022.58.12.3474538. PMID- 36402146 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230103 IS - 2352-3026 (Electronic) IS - 2352-3026 (Linking) VI - 10 IP - 1 DP - 2023 Jan TI - Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. PG - e24-e34 LID - S2352-3026(22)00319-2 [pii] LID - 10.1016/S2352-3026(22)00319-2 [doi] AB - BACKGROUND: Ponatinib and blinatumomab are effective therapies in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia, and their combination might be a promising treatment option. In this study, we aimed to evaluate this chemotherapy-free strategy. METHODS: We did a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center, Houston, TX, USA, in patients aged 18 years or older with newly diagnosed or relapsed or refractory Ph-positive acute lymphoblastic leukaemia or chronic myeloid leukaemia in lymphoid blast phase. Patients with an ECOG performance status of 2 or less who had a total bilirubin concentration two-times the upper limit of normal (ULN) or less (≤2·4 mg/dL), alanine aminotransferase and aspartate aminotransferase concentration no more than three-times the ULN, and serum lipase and amylase concentrations no more than three-times the ULN were eligible for inclusion. Ponatinib 30 mg orally and continuous intravenous blinatumomab 28 μg over 24 h (for 28 days each cycle) were given in combination for up to five 42-day cycles, followed by ponatinib monotherapy. Patients received 12 doses of intrathecal chemotherapy as CNS prophylaxis. The primary endpoints were complete molecular response (defined as absence of a detectable BCR-ABL1 transcript by PCR at a sensitivity of 0·01%) in patients with newly diagnosed disease and overall response in patients with relapsed or refractory disease or chronic myeloid leukaemia in lymphoid blast phase. All assessments were done according to the intention-to-treat principle. The trial completed its original target accrual and was amended on March 23, 2022, to enrol an additional 30 patients, thus increasing the sample size to 90 patients. The trial is registered with ClinicalTrials.gov, NCT03263572, and it is ongoing. FINDINGS: Between Feb 6, 2018, to May 6, 2022, 60 (83%) of 72 patients assessed were enrolled and received ponatinib and blinatumomab (40 [67%] patients had newly diagnosed Ph-positive acute lymphoblastic leukaemia, 14 [23%] had relapsed or refractory Ph-positive acute lymphoblastic leukaemia, and six [10%] had chronic myeloid leukaemia in lymphoid blast phase). 32 (53%) patients were men and 28 (47%) were women; 51 (85%) patients were White or Hispanic; and the median age of participants was 51 years (IQR 36-68). The median duration of follow-up for the entire cohort was 16 months (IQR 11-24). Of patients with newly diagnosed Ph-positive acute lymphoblastic leukaemia, 33 (87%) of 38 evaluable patients had a complete molecular response. 12 (92%) of 13 evaluable patients with relapsed or refractory Ph-positive acute lymphoblastic leukaemia had an overall response. 11 (79%) had a complete molecular response. Five (83%) of six patients with chronic myeloid leukaemia in lymphoid blast phase had an overall response. Two (33%) had a complete molecular response. The most common grade 3-4 adverse events that occurred in more than 5% of patients were infection (22 [37%] patients), increased amylase or lipase concentration (five [8%] patients), increased alanine aminotransferase or aspartate aminotransferase concentration (four [7%] patients), pain (four [7%] patients), and hypertension (four [7%] patients). One (2%) patient discontinued blinatumomab due to tremor. Three (5%) patients discontinued ponatinib secondary to cerebrovascular ischaemia, portal vein thrombosis, and coronary artery stenosis in one patient each. No treatment-related deaths were observed. INTERPRETATION: The chemotherapy-free combination of ponatinib and blinatumomab resulted in high rates of complete molecular response in patients with newly diagnosed and relapsed or refractory Ph-positive acute lymphoblastic leukaemia. Patients with newly diagnosed Ph-positive acute lymphoblastic leukaemia could be spared the toxicities associated with chemotherapy and the need for allogeneic haematopoietic stem-cell transplantation in first response. FUNDING: Takeda Oncology and Amgen. CI - Copyright © 2023 Elsevier Ltd. All rights reserved. FAU - Jabbour, Elias AU - Jabbour E AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ejabbour@mdanderson.org. FAU - Short, Nicholas J AU - Short NJ AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Jain, Nitin AU - Jain N AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Huang, Xuelin AU - Huang X AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Montalban-Bravo, Guillermo AU - Montalban-Bravo G AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Banerjee, Pinaki AU - Banerjee P AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Rezvani, Katayoun AU - Rezvani K AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Jiang, Xianli AU - Jiang X AD - Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kim, Kun Hee AU - Kim KH AD - Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kanagal-Shamanna, Rashmi AU - Kanagal-Shamanna R AD - Department of Hematopathology and Molecular Diagnostics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Khoury, Joseph D AU - Khoury JD AD - Department of Hematopathology and Molecular Diagnostics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Patel, Keyur AU - Patel K AD - Department of Hematopathology and Molecular Diagnostics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kadia, Tapan M AU - Kadia TM AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Daver, Naval AU - Daver N AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Chien, Kelly AU - Chien K AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Alvarado, Yesid AU - Alvarado Y AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Garcia-Manero, Guillermo AU - Garcia-Manero G AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Issa, Ghayas C AU - Issa GC AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Haddad, Fadi G AU - Haddad FG AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kwari, Monica AU - Kwari M AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Thankachan, Jennifer AU - Thankachan J AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Delumpa, Ricardo AU - Delumpa R AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Macaron, Walid AU - Macaron W AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Garris, Rebecca AU - Garris R AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Konopleva, Marina AU - Konopleva M AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ravandi, Farhad AU - Ravandi F AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kantarjian, Hagop AU - Kantarjian H AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT03263572 PT - Clinical Trial, Phase II PT - Journal Article DEP - 20221116 PL - England TA - Lancet Haematol JT - The Lancet. Haematology JID - 101643584 RN - 4340891KFS (ponatinib) RN - 4FR53SIF3A (blinatumomab) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM CIN - Lancet Haematol. 2023 Jan;10(1):e3-e5. PMID: 36402147 MH - Male MH - Humans MH - Female MH - Adult MH - Middle Aged MH - Aged MH - Philadelphia Chromosome MH - Blast Crisis/drug therapy/etiology MH - Alanine Transaminase/therapeutic use MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects COIS- Declaration of interests EJ reports research grants from Abbvie, Adaptive Biotechnologies, Amgen, Pfizer, and Takeda; and consultancy fees from Abbvie, Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Genentech, Incyte, Novartis, Pfizer, and Takeda. NJS reports research grants from Takeda Oncology, Astellas Pharma, Xencor, and Stemline Therapeutics; consultancy fees from Pfizer and Jazz Pharmaceuticals; and honoraria from Novartis, Amgen, Sanofi, and BeiGene. ND reports research funding from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, Gilead, Sevier, Genentech, Astellas, Daiichi-Sankyo, Abbvie, Hanmi, Trovagene, FATE therapeutics, Amgen, Novimmune, Glycomimetics, Trillium, and ImmunoGen; and served in a consulting or advisory role for Daiichi-Sankyo, Bristol-Myers Squibb, Arog, Pfizer, Novartis, Jazz, Celgene, AbbVie, Astellas, Genentech, Immunogen, Servier, Syndax, Trillium, Gilead, Amgen, Shattuck labs, and Agios. GCI reports research funding from Celgene, Kura Oncology, Syndax, and Novartis; and consultancy fees from Novartis and Kura Oncology. MK reports research funding from AbbVie, Genentech, F Hoffman La-Roche, Eli Lilly, Cellectis, Calithera, Ablynx, Stemline Therapeutics, Agios, Ascentage, AstraZeneca, Rafael Pharmaceutical, Sanofi, and Forty-Seven; consultancy fees or honoraria from AbbVie, Genentech, F Hoffman La-Roche, Stemline Therapeutics, Amgen, Forty-Seven, Kisoji, and Janssen; is on the advisory board for Stemline Therapeutics, F Hoffman La-Roche, and Janssen; and has stocks or royalties in Reata Pharmaceutical, Novartis, and Eli Lilly. HK reports research grants from AbbVie, Amgen, Ascentage, Bristol Myers Squibb, Daiichi-Sankyo, Immunogen, Jazz, Novartis, and Pfizer; and honoraria from AbbVie, Amgen, Aptitude Health, Ascentage, Astellas Health, Astra Zeneca, Ipsen, Pharmaceuticals, KAHR Medical, NOVA Research, Novartis, Pfizer, Precision Biosciences, and Taiho Pharmaceutical Canada. All other authors declare no competing interests. EDAT- 2022/11/20 06:00 MHDA- 2022/12/28 06:00 CRDT- 2022/11/19 19:06 PHST- 2022/09/02 00:00 [received] PHST- 2022/09/14 00:00 [revised] PHST- 2022/09/15 00:00 [accepted] PHST- 2022/11/20 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/11/19 19:06 [entrez] AID - S2352-3026(22)00319-2 [pii] AID - 10.1016/S2352-3026(22)00319-2 [doi] PST - ppublish SO - Lancet Haematol. 2023 Jan;10(1):e24-e34. doi: 10.1016/S2352-3026(22)00319-2. Epub 2022 Nov 16. PMID- 36641658 OWN - NLM STAT- MEDLINE DCOM- 20230117 LR - 20230117 IS - 1558-1551 (Electronic) IS - 0888-6008 (Linking) VI - 41 IP - 1 DP - 2022 TI - Platelet count and breast cancer stage. PG - 489-493 LID - 10.3233/BD-229007 [doi] AB - INTRODUCTION: The relationship between increased platelet count and cancer classification stage has long been established. The prevalence of thrombocytosis varies from 10% to 57% in cancer patients. The pathogenesis of thrombocytosis in malignancy is uncertain. However, there is evidence that tumor cells secrete humoral factors that can cause thrombocytosis. Preoperative thrombocytosis is a poor prognostic variable in malignancies. This study investigated the correlation between platelet count and breast cancer stage. METHODS: This cross-sectional study was conducted from February 2020 to January 2021. Patient data were collected from medical records. The study population comprised breast cancer patients at Dr. Wahidin Sudirohusodo Makassar. The staging examinations were based on the tumor, node, metastasis (TNM) classification according to the American Joint Committee on Cancer (AJCC) 8th Edition. RESULTS: The study group comprised 171 breast cancer patients of varying ages. Metastasis was present in five (2.92%) patients and absent in 166 (97.8%) patients. Analyses found no statistically significant differences between the three staging groups based on the platelet count (p = 0.952). CONCLUSION: There was no statistically significant relationship between increased platelet count and staging according to the TNM classification in breast cancer patients. FAU - Fahdrin, Andi AU - Fahdrin A AD - Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Sampepajung, Elridho AU - Sampepajung E AD - Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Pieter, John AU - Pieter J AD - Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Kasim, Firdaus AU - Kasim F AD - Department of Biostatistics, Faculty of Public Health, Hasanuddin University, Makassar, Indonesia. FAU - Smaradhania, Nilam AU - Smaradhania N AD - Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Prihantono, Prihantono AU - Prihantono P AD - Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Mariana, Nita AU - Mariana N AD - Division of Pediatric Surgery, Department of Surgery, Hasanuddin University, >Makassar, Indonesia. FAU - Sampepajung, Daniel AU - Sampepajung D AD - Division of Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. FAU - Faruk, Muhammad AU - Faruk M AD - Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. LA - eng PT - Journal Article PL - Netherlands TA - Breast Dis JT - Breast disease JID - 8801277 SB - IM MH - Humans MH - Female MH - Platelet Count MH - *Breast Neoplasms/pathology MH - Cross-Sectional Studies MH - Retrospective Studies MH - Prognosis MH - Neoplasm Staging MH - *Thrombocytosis/pathology OTO - NOTNLM OT - American Joint Committee on Cancer OT - breast cancer OT - platelet counts OT - staging EDAT- 2023/01/16 06:00 MHDA- 2023/01/18 06:00 CRDT- 2023/01/15 05:22 PHST- 2023/01/15 05:22 [entrez] PHST- 2023/01/16 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] AID - BD229007 [pii] AID - 10.3233/BD-229007 [doi] PST - ppublish SO - Breast Dis. 2022;41(1):489-493. doi: 10.3233/BD-229007. PMID- 36481960 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230111 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 117 IP - 1 DP - 2023 Jan TI - Chronic myeloid leukemia: the cutting-edge evidence and things we should know. PG - 1-2 LID - 10.1007/s12185-022-03511-9 [doi] AB - The prognosis of patients with chronic myeloid leukemia has dramatically improved along with the progress of therapy. However, some concerns remain unresolved, and new treatment strategies have been implemented recently. In this Progress in Hematology corner, the following four issues are presented and discussed: (1) Guidelines for the treatment of chronic myeloid leukemia from the NCCN and ELN: Differences and similarities; (2) Asciminib as a third-line option in chronic myeloid leukemia; (3) Dose optimization of tyrosine kinase inhibitor therapy in chronic myeloid leukemia; and (4) Genetic landscape of chronic myeloid leukemia. All these review articles will provide critical information for hematologists and let us know things we should learn in order to treat patients with this disease adequately. CI - © 2022. Japanese Society of Hematology. FAU - Iriyama, Noriyoshi AU - Iriyama N AUID- ORCID: 0000-0001-9176-1988 AD - Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi-Ku, Tokyo, 173-8610, Japan. iriyama.noriyoshi@nihon-u.ac.jp. LA - eng PT - Editorial DEP - 20221208 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Humans MH - Protein Kinase Inhibitors/therapeutic use/pharmacology MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics MH - Prognosis MH - *Hematology MH - Molecular Targeted Therapy EDAT- 2022/12/10 06:00 MHDA- 2023/01/07 06:00 CRDT- 2022/12/09 00:25 PHST- 2022/12/05 00:00 [received] PHST- 2022/12/05 00:00 [accepted] PHST- 2022/12/05 00:00 [revised] PHST- 2022/12/10 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/12/09 00:25 [entrez] AID - 10.1007/s12185-022-03511-9 [pii] AID - 10.1007/s12185-022-03511-9 [doi] PST - ppublish SO - Int J Hematol. 2023 Jan;117(1):1-2. doi: 10.1007/s12185-022-03511-9. Epub 2022 Dec 8. PMID- 36469102 OWN - NLM STAT- MEDLINE DCOM- 20230123 LR - 20230123 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 482 IP - 1 DP - 2023 Jan TI - Advances in myelodysplastic/myeloproliferative neoplasms. PG - 69-83 LID - 10.1007/s00428-022-03465-7 [doi] AB - The myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) category includes a heterogeneous group of diseases characterized by the co-occurrence of clinical and pathologic features of both myelodysplastic and myeloproliferative neoplasms. The recently published International Consensus Classification of myeloid neoplasms revised the entities included in the MDS/MPN category as well as criteria for their diagnosis. In addition to the presence of one or more increased peripheral blood cell counts as evidence of myeloproliferative features, concomitant cytopenia as evidence of ineffective hematopoiesis is now an explicit requirement to diagnose the diseases included in this category. The increasing availability of modern gene sequencing has allowed better understanding of the biologic characteristics of these myeloid neoplasms. The presence of specific mutations in the appropriate clinicopathologic context is now included in the diagnostic criteria for some of MDS/MPN entities. In this review, we highlight what has changed in the diagnostic criteria of MDS/MPN from the WHO 2016 classification while providing practical guidance in diagnosing these diseases. CI - © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Prakash, Sonam AU - Prakash S AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. FAU - Arber, Daniel A AU - Arber DA AD - Department of Pathology, University of Chicago, Chicago, IL, USA. FAU - Bueso-Ramos, Carlos AU - Bueso-Ramos C AD - Division of Pathology and Laboratory Medicine, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Hasserjian, Robert P AU - Hasserjian RP AD - Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Orazi, Attilio AU - Orazi A AUID- ORCID: 0000-0002-1660-7013 AD - Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX, USA. Attilio.Orazi@ttuhsc.edu. LA - eng PT - Journal Article PT - Review DEP - 20221205 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 SB - IM MH - Humans MH - *Neoplasms MH - *Myelodysplastic-Myeloproliferative Diseases/diagnosis/genetics MH - *Myeloproliferative Disorders/diagnosis/genetics/pathology MH - Mutation/genetics OTO - NOTNLM OT - Atypical chronic myeloid leukemia OT - Chronic myelomonocytic leukemia OT - Myelodysplastic/myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis OT - Myelodysplastic/myeloproliferative neoplasm with isolated i(17q) OT - Myelodysplastic/myeloproliferative neoplasms EDAT- 2022/12/06 06:00 MHDA- 2023/01/24 06:00 CRDT- 2022/12/05 11:14 PHST- 2022/08/18 00:00 [received] PHST- 2022/11/23 00:00 [accepted] PHST- 2022/11/22 00:00 [revised] PHST- 2022/12/06 06:00 [pubmed] PHST- 2023/01/24 06:00 [medline] PHST- 2022/12/05 11:14 [entrez] AID - 10.1007/s00428-022-03465-7 [pii] AID - 10.1007/s00428-022-03465-7 [doi] PST - ppublish SO - Virchows Arch. 2023 Jan;482(1):69-83. doi: 10.1007/s00428-022-03465-7. Epub 2022 Dec 5. PMID- 36477676 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230111 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 117 IP - 1 DP - 2023 Jan TI - Genetic landscape of chronic myeloid leukemia. PG - 30-36 LID - 10.1007/s12185-022-03510-w [doi] AB - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the BCR::ABL1 fusion gene, which aberrantly activates ABL1 kinase and promotes the overproduction of leukemic cells. CML typically develops in the chronic phase (CP) and progresses to a blast crisis (BC) after years without effective treatment. Although prognosis has substantially improved after the development of tyrosine kinase inhibitors (TKIs) targeting the BCR::ABL1 oncoprotein, some patients still experience TKI resistance and poor prognosis. One of the mechanisms of TKI resistance is ABL1 kinase domain mutations, which are found in approximately half of the cases, newly acquired during treatment. Moreover, genetic studies have revealed that CML patients carry additional mutations that are also observed in other myeloid neoplasms. ASXL1 mutations are often found in both CP and BC, whereas other mutations, such as those in RUNX1, IKZF1, and TP53, are preferentially found in BC. The presence of additional mutations, such as ASXL1 mutations, is a potential biomarker for predicting therapeutic efficacy. The mechanisms by which these additional mutations affect disease subtypes, drug resistance, and prognosis need to be elucidated. In this review, we have summarized and discussed the landscape and clinical impact of genetic abnormalities in CML. CI - © 2022. Japanese Society of Hematology. FAU - Ochi, Yotaro AU - Ochi Y AUID- ORCID: 0000-0001-8472-6164 AD - Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, F-Building, Yoshida-Konoe-Cho, Sakyo-Ku, Kyoto, 606-8501, Japan. ochi.yotaro.24v@kyoto-u.jp. LA - eng PT - Journal Article PT - Review DEP - 20221207 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Humans MH - *Fusion Proteins, bcr-abl/genetics MH - Protein Kinase Inhibitors/pharmacology/therapeutic use MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics MH - Blast Crisis/drug therapy MH - Mutation MH - Drug Resistance, Neoplasm/genetics OTO - NOTNLM OT - Chronic myeloid leukemia OT - Clonal evolution OT - Genetics OT - Precision medicine EDAT- 2022/12/09 06:00 MHDA- 2023/01/07 06:00 CRDT- 2022/12/08 12:09 PHST- 2022/11/28 00:00 [received] PHST- 2022/12/04 00:00 [accepted] PHST- 2022/12/01 00:00 [revised] PHST- 2022/12/09 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/12/08 12:09 [entrez] AID - 10.1007/s12185-022-03510-w [pii] AID - 10.1007/s12185-022-03510-w [doi] PST - ppublish SO - Int J Hematol. 2023 Jan;117(1):30-36. doi: 10.1007/s12185-022-03510-w. Epub 2022 Dec 7. PMID- 36611899 OWN - NLM STAT- MEDLINE DCOM- 20230118 LR - 20230118 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 12 IP - 1 DP - 2022 Dec 27 TI - Impact of Molecular Biology in Diagnosis, Prognosis, and Therapeutic Management of BCR::ABL1-Negative Myeloproliferative Neoplasm. LID - 10.3390/cells12010105 [doi] LID - 105 AB - BCR::ABL1-negative myeloproliferative neoplasms (MPNs) include three major subgroups-polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)-which are characterized by aberrant hematopoietic proliferation with an increased risk of leukemic transformation. Besides the driver mutations, which are JAK2, CALR, and MPL, more than twenty additional mutations have been identified through the use of next-generation sequencing (NGS), which can be involved with pathways that regulate epigenetic modifications, RNA splicing, or DNA repair. The aim of this short review is to highlight the impact of molecular biology on the diagnosis, prognosis, and therapeutic management of patients with PV, ET, and PMF. FAU - Abbou, Norman AU - Abbou N AD - Molecular Biology Laboratory, North University Hospital, 13015 Marseille, France. AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. FAU - Piazzola, Pauline AU - Piazzola P AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. FAU - Gabert, Jean AU - Gabert J AD - Molecular Biology Laboratory, North University Hospital, 13015 Marseille, France. AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. FAU - Ernest, Vincent AU - Ernest V AD - Hematology Laboratory, Timone University Hospital, 13005 Marseille, France. FAU - Arcani, Robin AU - Arcani R AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. AD - Department of Internal Medicine, Timone University Hospital, 13005 Marseille, France. FAU - Couderc, Anne-Laure AU - Couderc AL AUID- ORCID: 0000-0003-2938-2201 AD - Department of Geriatrics, South University Hospital, 13005 Marseille, France. FAU - Tichadou, Antoine AU - Tichadou A AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. FAU - Roche, Pauline AU - Roche P AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. FAU - Farnault, Laure AU - Farnault L AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. FAU - Colle, Julien AU - Colle J AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. FAU - Ouafik, L'houcine AU - Ouafik L AD - CNRS, INP, Institute of Neurophysiopathol, Aix-Marseille Université, 13005 Marseille, France. AD - APHM, CHU Nord, Service d'Onco-Biologie, Aix-Marseille Université, 13005 Marseille, France. FAU - Morange, Pierre AU - Morange P AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. AD - Hematology Laboratory, Timone University Hospital, 13005 Marseille, France. FAU - Costello, Régis AU - Costello R AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. AD - TAGC, INSERM, UMR1090, Aix-Marseille University, 13005 Marseille, France. FAU - Venton, Geoffroy AU - Venton G AD - INSERM, INRAE, C2VN, Aix-Marseille University, 13005 Marseille, France. AD - Hematology and Cellular Therapy Department, Conception University Hospital, 13005 Marseille, France. AD - TAGC, INSERM, UMR1090, Aix-Marseille University, 13005 Marseille, France. LA - eng PT - Journal Article PT - Review DEP - 20221227 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Calreticulin) RN - 0 (Receptors, Thrombopoietin) RN - 0 (abl-bcr fusion protein, human) SB - IM MH - Humans MH - Calreticulin/genetics/metabolism MH - Molecular Biology MH - *Myeloproliferative Disorders/diagnosis/genetics/therapy MH - *Polycythemia Vera/genetics MH - Receptors, Thrombopoietin/genetics/metabolism MH - *Thrombocythemia, Essential/genetics PMC - PMC9818322 OTO - NOTNLM OT - additional somatic mutations OT - driver mutations OT - myeloproliferative neoplasms OT - next-generation sequencing COIS- The authors declare no conflict of interest. EDAT- 2023/01/09 06:00 MHDA- 2023/01/11 06:00 CRDT- 2023/01/08 01:06 PHST- 2022/11/08 00:00 [received] PHST- 2022/12/16 00:00 [revised] PHST- 2022/12/23 00:00 [accepted] PHST- 2023/01/08 01:06 [entrez] PHST- 2023/01/09 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] AID - cells12010105 [pii] AID - cells-12-00105 [pii] AID - 10.3390/cells12010105 [doi] PST - epublish SO - Cells. 2022 Dec 27;12(1):105. doi: 10.3390/cells12010105. PMID- 36580008 OWN - NLM STAT- MEDLINE DCOM- 20230102 LR - 20230103 IS - 2476-762X (Electronic) IS - 1513-7368 (Linking) VI - 23 IP - 12 DP - 2022 Dec 1 TI - Inequality in Drug Utilization among Chronic Myeloid Leukaemia Patients in Malaysia: A Cost-Utility Analysis. PG - 4253-4260 LID - 90431 [pii] LID - 10.31557/APJCP.2022.23.12.4253 [doi] AB - BACKGROUND: The burden of chronic myeloid leukaemia (CML) is increasing due to longer patient survival, better life expectancy of the general population, and increasing drug prices. Funding is one of the main concerns in the choice of CML medication used worldwide; thus, patient assistance programmes were introduced to ensure accessibility to affordable treatment. In this study, we evaluated CML drug distribution inequality in Malaysia through patient assistance programmes, using pharmaco-economics methods to evaluate CML treatment from the care provider's perspective. METHODS: Patients with CML were recruited from outpatient haematological clinics at the national centre of intervention and referral for haematological conditions and a public teaching hospital. The health-related quality of life or utility scores were derived using the EuroQol EQ-5D-5L questionnaire. Costing data were obtained from the Ministry of Health Malaysia Casemix MalaysianDRG. Imatinib and nilotinib drug costs were obtained from the administration of the participating hospitals and pharmaceutical company. RESULTS: Of the 221 respondents in this study, 68.8% were imatinib users. The total care provider cost for CML treatment was USD23,014.40 for imatinib and USD43,442.69 for nilotinib. The governmental financial assistance programme reduced the total care provider cost to USD13,693.51 for imatinib and USD19,193.45 for nilotinib. The quality-adjusted life years (QALYs) were 17.87 and 20.91 per imatinib and nilotinib user, respectively. Nilotinib had a higher drug cost than imatinib, yet its users had better life expectancy, utility score, and QALYs. Imatinib yielded the lowest cost per QALYs at USD766.29. CONCLUSION: Overall, imatinib is more cost-effective than nilotinib for treating CML in Malaysia from the care provider's perspective. The findings demonstrate the importance of cancer drug funding assistance for ensuring that the appropriate treatments are accessible and affordable and that patients with cancer use and benefit from such patient assistance programmes. To establish effective health expenditure, drug distribution inequality should be addressed. FAU - Wan Puteh, Sharifa Ezat AU - Wan Puteh SE AUID- ORCID: 0000-0001-6251-2528 AD - Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. FAU - Mohamad Selamat, Ellyana AU - Mohamad Selamat E AUID- ORCID: 0000-0003-2399-0193 AD - Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. FAU - Aizuddin, Azimatun Noor AU - Aizuddin AN AUID- ORCID: 0000-0001-8050-4150 AD - Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. FAU - Tumian, Nor Rafeah AU - Tumian NR AUID- ORCID: 0000-0001-6124-8120 AD - Department of Medicine, Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia. FAU - Sathar, Jameela AU - Sathar J AUID- ORCID: 0000-0003-1943-0863 AD - Department of Haematology, Hospital Ampang, Ministry of Health Malaysia, Kuala Lumpur, Malaysia. LA - eng PT - Journal Article DEP - 20221201 PL - Thailand TA - Asian Pac J Cancer Prev JT - Asian Pacific journal of cancer prevention : APJCP JID - 101130625 RN - 8A1O1M485B (Imatinib Mesylate) RN - RBZ1571X5H (Dasatinib) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Antineoplastic Agents) RN - 0 (Pyrimidines) SB - IM MH - Humans MH - Imatinib Mesylate/therapeutic use MH - Dasatinib/therapeutic use MH - Cost-Benefit Analysis MH - Quality of Life MH - Malaysia/epidemiology MH - Protein Kinase Inhibitors/therapeutic use MH - *Antineoplastic Agents/therapeutic use MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy MH - Pyrimidines/adverse effects MH - Chronic Disease MH - Drug Utilization OTO - NOTNLM OT - Chronic Myeloid Leukaemia OT - Nilotinib OT - cost effectiveness analysis OT - imatinib OT - tyrosine kinase inhibitors EDAT- 2022/12/30 06:00 MHDA- 2023/01/03 06:00 CRDT- 2022/12/29 10:05 PHST- 2022/07/29 00:00 [received] PHST- 2022/12/29 10:05 [entrez] PHST- 2022/12/30 06:00 [pubmed] PHST- 2023/01/03 06:00 [medline] AID - 90431 [pii] AID - 10.31557/APJCP.2022.23.12.4253 [doi] PST - epublish SO - Asian Pac J Cancer Prev. 2022 Dec 1;23(12):4253-4260. doi: 10.31557/APJCP.2022.23.12.4253. PMID- 36567324 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230103 IS - 1472-6963 (Electronic) IS - 1472-6963 (Linking) VI - 22 IP - 1 DP - 2022 Dec 26 TI - Cost-effectiveness analysis of dasatinib versus imatinib in pediatric philadelphia chromosome-positive acute lymphoblastic leukemia patients in China. PG - 1580 LID - 10.1186/s12913-022-08971-7 [doi] LID - 1580 AB - BACKGROUND: Dasatinib and imatinib are the recommended tyrosine kinase inhibitors (TKIs) for treating pediatric Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL), and the one which has been approved indication in China is imatinib. Recently, clinical demand for Ph + ALL treatment is becoming unmet gradually with the increasing resistance of imatinib. There are some studies reporting the better efficacy and comparative safety of dasatinib compared with imatinib, but no economic comparison has been published. This study aims to supplement economic evidence by comparing the cost-effectiveness between imatinib and dasatinib in treating pediatric patients with Ph+ ALL in China, and to help clinical rational drug use via multi-dimensional value assessment. METHODS: A decision tree model combined with a 10-year Markov model were established based on the disease progression. The parameters were collected from published literatures and our hospital's electronic medical records. From the health system perspective, the incremental cost-effectiveness ratio (ICER) between the two treatment groups was calculated through cost-effectiveness analysis and then compared with the willingness-to-pay (WTP) threshold. The set WTP threshold in this study was 1 times per capita gross domestic product (GDP) of China, as recommended by the World Health Organization. Direct medical costs and quality-adjusted life years (QALYs) were calculated and discounted at 5%. The sensitivity analyses were conducted to assess the uncertainty and robustness of the results. RESULTS: The total costs were CNY 1,020,995.35 and CNY 1,035,788.50 in imatinib group and dasatinib group during the 10-year simulation, and the total QALYs were 2.59 and 4.84. Compared with the imatinib treatment group, the ICER was around CNY 6,575.78/ QALY, which was less than the set threshold CNY 70,892/ QALY. The sensitive analyses indicated the robustness of the results. CONCLUSIONS: The cost-effectiveness analysis shows the potential cost-effective advantages of adding dasatinib comparing with adding imatinib for pediatric Ph + ALL patients in China under the set WTP threshold, which indicates that those patients could achieve more QALYs by paying acceptable fee. CI - © 2022. The Author(s). FAU - Cao, Wang AU - Cao W AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. AD - Department of Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. FAU - Yu, Yuncui AU - Yu Y AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. AD - Department of Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. FAU - Qiu, Yingpeng AU - Qiu Y AD - National Health Development Research Center, National Health Commission, Beijing, China. AD - University of Sheffield, Sheffield, UK. FAU - Liu, Lu AU - Liu L AD - Department of Pharmacy, Qingdao Women and Children's Hospital, Qingdao, China. FAU - Zhang, Hao AU - Zhang H AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. FAU - Shi, Liwei AU - Shi L AD - National Health Development Research Center, National Health Commission, Beijing, China. FAU - Xiao, Yue AU - Xiao Y AD - National Health Development Research Center, National Health Commission, Beijing, China. FAU - Jia, Lulu AU - Jia L AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. jluyu@126.com. AD - Department of Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. jluyu@126.com. FAU - Zhang, Ruidong AU - Zhang R AD - Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. zhangruidong@vip.sina.com. FAU - Wang, Xiaoling AU - Wang X AD - Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. wangxiaoling@bch.com.cn. LA - eng PT - Journal Article DEP - 20221226 PL - England TA - BMC Health Serv Res JT - BMC health services research JID - 101088677 RN - 8A1O1M485B (Imatinib Mesylate) RN - RBZ1571X5H (Dasatinib) RN - 0 (Pyrimidines) RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Humans MH - Child MH - Imatinib Mesylate/therapeutic use MH - Dasatinib/therapeutic use MH - *Cost-Effectiveness Analysis MH - Philadelphia Chromosome MH - Pyrimidines/therapeutic use MH - Protein Kinase Inhibitors/therapeutic use MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy MH - Cost-Benefit Analysis MH - China MH - Quality-Adjusted Life Years PMC - PMC9791740 OTO - NOTNLM OT - Children OT - Cost-effectiveness analysis OT - Dasatinib OT - Imatinib OT - Philadelphia-positive acute lymphoblastic leukemia COIS- The authors declare that they have no competing interests. EDAT- 2022/12/26 06:00 MHDA- 2022/12/28 06:00 CRDT- 2022/12/25 23:13 PHST- 2022/05/03 00:00 [received] PHST- 2022/12/14 00:00 [accepted] PHST- 2022/12/25 23:13 [entrez] PHST- 2022/12/26 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] AID - 10.1186/s12913-022-08971-7 [pii] AID - 8971 [pii] AID - 10.1186/s12913-022-08971-7 [doi] PST - epublish SO - BMC Health Serv Res. 2022 Dec 26;22(1):1580. doi: 10.1186/s12913-022-08971-7. PMID- 36087226 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230111 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 117 IP - 1 DP - 2023 Jan TI - Dose optimization of tyrosine kinase inhibitor therapy in chronic myeloid leukemia. PG - 24-29 LID - 10.1007/s12185-022-03431-8 [doi] AB - The therapeutic outcomes of chronic myeloid leukemia (CML) have improved dramatically since tyrosine kinase inhibitors (TKIs) became available in clinical practice. Life expectancy of patients with CML is now close to that of the general population. Patients with CML who achieve sustained deep molecular response may discontinue TKI therapy. However, most patients still require TKI therapy for long periods without sustained deep molecular response. Given the awareness of increased incidence of arterial occlusive events in patients on TKI therapy, the optimal TKI selection should be based on age, comorbidities, risk classification, and goals of treatment. Dose optimization of TKI therapy reduces the incidence of adverse events while maintaining efficacy in CML. CI - © 2022. Japanese Society of Hematology. FAU - Umezawa, Yoshihiro AU - Umezawa Y AD - Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. FAU - Sasaki, Koji AU - Sasaki K AUID- ORCID: 0000-0002-9140-0610 AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX, 77030, USA. ksasaki1@mdanderson.org. LA - eng PT - Journal Article PT - Review DEP - 20220910 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - 0 (Tyrosine Protein Kinase Inhibitors) RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Humans MH - *Tyrosine Protein Kinase Inhibitors MH - Protein Kinase Inhibitors/adverse effects MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy MH - Molecular Targeted Therapy OTO - NOTNLM OT - CML OT - Dose optimization OT - Tyrosine kinase inhibitor EDAT- 2022/09/11 06:00 MHDA- 2023/01/07 06:00 CRDT- 2022/09/10 11:19 PHST- 2022/06/28 00:00 [received] PHST- 2022/07/26 00:00 [accepted] PHST- 2022/07/26 00:00 [revised] PHST- 2022/09/11 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/09/10 11:19 [entrez] AID - 10.1007/s12185-022-03431-8 [pii] AID - 10.1007/s12185-022-03431-8 [doi] PST - ppublish SO - Int J Hematol. 2023 Jan;117(1):24-29. doi: 10.1007/s12185-022-03431-8. Epub 2022 Sep 10. PMID- 36557000 OWN - NLM STAT- MEDLINE DCOM- 20221226 LR - 20221226 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 58 IP - 12 DP - 2022 Dec 6 TI - Essential Thrombocythemia: One-Center Data in a Changing Disease. LID - 10.3390/medicina58121798 [doi] LID - 1798 AB - Introduction: Essential thrombocythemia is a chronic myeloproliferative neoplasm associated with thrombo-hemorrhagic events and the progression to myelofibrosis or acute myeloid leukemia. The purpose of this article is to present real-world data on ET cases diagnosed and managed between 1998 and 2020 in the largest, tertiary hematology reference center in Romania and to evaluate the impact of thrombotic events on survival. Methods: A real-world, retrospective cohort-type study was conducted. We collected and statistically analyzed data from 168 patients who met the 2016 WHO diagnostic criteria for ET and who were managed between 1998 and 2020 in our center. Results: The median age at diagnosis of ET was 51.8 years, with a female predominance (66.07%). The JAK2V617F mutation was detected in 60.71% of patients. Leukocytosis at diagnosis was associated with a higher risk of thrombosis, and JAK2V617F-positive cases exhibited a 1.5-fold higher risk of developing thrombotic events. The average survival in ET with major thrombosis was 14.5 years versus 20.6 years in ET cases without major thrombosis. Other predictors of survival were high-risk IPSET score and age >60 years. Conclusions: Romanian patients diagnosed with ET are generally younger than 60 years and are predominantly female. The occurrence of thrombotic events was influenced by gender, leukocyte count at diagnosis and JAK2V617F positivity. Survival was impacted by age, the presence of JAK2V617F mutation, hypertension, major thrombotic complications and IPSET score. Notably, these findings warrant careful interpretation and further confirmation in the setting of prospective studies. FAU - Pirciulescu, Nicoleta AU - Pirciulescu N AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. FAU - Gaman, Mihnea-Alexandru AU - Gaman MA AUID- ORCID: 0000-0001-7133-8875 AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. AD - Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania. FAU - Mihailescu, Marina AU - Mihailescu M AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. FAU - Constantin, Cristina AU - Constantin C AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. FAU - Dragomir, Mihaela AU - Dragomir M AD - Department of Molecular Biology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. FAU - Dobrea, Camelia AU - Dobrea C AD - Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania. AD - Department of Hematopathology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. FAU - Costache, Simona AU - Costache S AD - Department of Cytomorphology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. FAU - Ursuleac, Iulia AU - Ursuleac I AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. AD - Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania. FAU - Coriu, Daniel AU - Coriu D AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. AD - Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania. FAU - Crisan, Ana Manuela AU - Crisan AM AD - Department of Clinical Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. AD - Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania. LA - eng PT - Journal Article DEP - 20221206 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 SB - IM MH - Humans MH - Female MH - Middle Aged MH - Male MH - *Thrombocythemia, Essential/complications/genetics MH - Retrospective Studies MH - Prospective Studies MH - Prognosis MH - *Thrombosis/etiology MH - Risk Factors MH - Mutation PMC - PMC9782858 OTO - NOTNLM OT - IPSET score OT - JAK2 OT - essential thrombocythemia OT - survival OT - thrombosis COIS- The authors declare no conflict of interest. EDAT- 2022/12/24 06:00 MHDA- 2022/12/27 06:00 CRDT- 2022/12/23 01:44 PHST- 2022/09/14 00:00 [received] PHST- 2022/12/01 00:00 [revised] PHST- 2022/12/02 00:00 [accepted] PHST- 2022/12/23 01:44 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/27 06:00 [medline] AID - medicina58121798 [pii] AID - medicina-58-01798 [pii] AID - 10.3390/medicina58121798 [doi] PST - epublish SO - Medicina (Kaunas). 2022 Dec 6;58(12):1798. doi: 10.3390/medicina58121798. PMID- 36580136 OWN - NLM STAT- MEDLINE DCOM- 20230123 LR - 20230123 IS - 1432-2307 (Electronic) IS - 0945-6317 (Print) IS - 0945-6317 (Linking) VI - 482 IP - 1 DP - 2023 Jan TI - International Consensus Classification of myeloid and lymphoid neoplasms: myeloproliferative neoplasms. PG - 53-68 LID - 10.1007/s00428-022-03480-8 [doi] AB - The recently published International Consensus Classification (ICC) of myeloid neoplasms summarized the results of an in-depth effort by pathologists, oncologists, and geneticists aimed to update the 2017 World Health Organization classification system for hematopoietic tumors. Along these lines, several important modifications were implemented in the classification of myeloproliferative neoplasms (MPNs). For chronic myeloid leukemia, BCR::ABL1-positive, the definition of accelerated and blast phase was simplified, and in the BCR::ABL1-negative MPNs, the classification was slightly updated to improve diagnostic specificity with a more detailed and better validated morphologic approach and the recommendation of more sensitive molecular techniques to capture in particular early stage diseases. In this regard, high sensitive single target (RT-qPCR, ddPCR) or multi-target next-generation sequencing assays with a minimal sensitivity of VAF 1% are now important for a proper diagnostic identification of MPN cases with low allelic frequencies at initial presentation. This review discusses the updated diagnostic criteria of MPN according to the ICC, particularly by highlighting the new concepts and how they can be applied in clinical settings to obtain an appropriate prognostic relevant diagnosis. CI - © 2022. The Author(s). FAU - Gianelli, Umberto AU - Gianelli U AD - University of Milan, Department of Health Sciences and S.C. Anatomia Patologica, ASST Santi Paolo e Carlo, Milan, Italy. FAU - Thiele, Jürgen AU - Thiele J AD - Institute of Pathology, University of Cologne, Cologne, Germany. FAU - Orazi, Attilio AU - Orazi A AD - Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX, USA. FAU - Gangat, Naseema AU - Gangat N AD - Mayo Clinic, Rochester, MN, USA. FAU - Vannucchi, Alessandro M AU - Vannucchi AM AD - CRIMM-Centro Ricerca e Innovazione delle Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. FAU - Tefferi, Ayalew AU - Tefferi A AD - Mayo Clinic, Rochester, MN, USA. FAU - Kvasnicka, Hans Michael AU - Kvasnicka HM AUID- ORCID: 0000-0002-5450-4840 AD - University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany. hm.kvasnicka@patho-uwh.de. LA - eng PT - Journal Article PT - Review DEP - 20221229 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 SB - IM MH - Humans MH - Consensus MH - *Myeloproliferative Disorders/diagnosis/genetics MH - *Lymphoma MH - *Hematologic Neoplasms PMC - PMC9852206 OTO - NOTNLM OT - International Consensus Classification OT - Myeloid and lymphoid neoplasms: Myeloproliferative neoplasms COIS- The authors declare no competing interests. EDAT- 2022/12/30 06:00 MHDA- 2023/01/24 06:00 CRDT- 2022/12/29 11:15 PHST- 2022/09/02 00:00 [received] PHST- 2022/12/16 00:00 [accepted] PHST- 2022/12/11 00:00 [revised] PHST- 2022/12/30 06:00 [pubmed] PHST- 2023/01/24 06:00 [medline] PHST- 2022/12/29 11:15 [entrez] AID - 10.1007/s00428-022-03480-8 [pii] AID - 3480 [pii] AID - 10.1007/s00428-022-03480-8 [doi] PST - ppublish SO - Virchows Arch. 2023 Jan;482(1):53-68. doi: 10.1007/s00428-022-03480-8. Epub 2022 Dec 29. PMID- 35930119 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230111 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 117 IP - 1 DP - 2023 Jan TI - Asciminib as a third line option in chronic myeloid leukemia. PG - 16-23 LID - 10.1007/s12185-022-03432-7 [doi] AB - Unmet needs remain in the treatment of chronic phase chronic myeloid leukemia (CML) in later lines. Sequential use of tyrosine kinase inhibitors (TKIs) is associated with decreased overall survival and emergence of new mutations, particularly the T315I mutation. Among the new drugs developed to overcome resistance and intolerance, the STAMP inhibitor asciminib (which specifically targets the ABL myristoyl pocket) is the first example of a drug that works by allosteric inhibition. This review focuses on its mechanism of action, pharmacokinetic, efficacy, and toxicity, as well as how this drug will change the therapeutic approach for CML patients not eligible to receive other available drugs. CI - © 2022. Japanese Society of Hematology. FAU - Laganà, Alessandro AU - Laganà A AD - Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Via Benevento 6, 00161, Rome, Italy. FAU - Scalzulli, Emilia AU - Scalzulli E AD - Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Via Benevento 6, 00161, Rome, Italy. FAU - Carmosino, Ida AU - Carmosino I AD - Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Via Benevento 6, 00161, Rome, Italy. FAU - Martelli, Maurizio AU - Martelli M AD - Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Via Benevento 6, 00161, Rome, Italy. FAU - Breccia, Massimo AU - Breccia M AUID- ORCID: 0000-0003-1163-6162 AD - Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Via Benevento 6, 00161, Rome, Italy. breccia@bce.uniroma1.it. LA - eng PT - Journal Article PT - Review DEP - 20220805 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - 0 (asciminib) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) RN - 0 (Pyrazoles) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Antineoplastic Agents) SB - IM MH - Humans MH - Drug Resistance, Neoplasm MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics MH - Fusion Proteins, bcr-abl/genetics MH - Pyrazoles/therapeutic use MH - Mutation MH - Protein Kinase Inhibitors/pharmacology/therapeutic use MH - *Antineoplastic Agents/adverse effects OTO - NOTNLM OT - Asciminib OT - Chronic myeloid leukemia OT - Later lines EDAT- 2022/08/06 06:00 MHDA- 2023/01/07 06:00 CRDT- 2022/08/05 11:17 PHST- 2022/07/09 00:00 [received] PHST- 2022/07/26 00:00 [accepted] PHST- 2022/07/26 00:00 [revised] PHST- 2022/08/06 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/08/05 11:17 [entrez] AID - 10.1007/s12185-022-03432-7 [pii] AID - 10.1007/s12185-022-03432-7 [doi] PST - ppublish SO - Int J Hematol. 2023 Jan;117(1):16-23. doi: 10.1007/s12185-022-03432-7. Epub 2022 Aug 5. PMID- 36349465 OWN - NLM STAT- MEDLINE DCOM- 20230112 LR - 20230112 IS - 1096-8652 (Electronic) IS - 0361-8609 (Linking) VI - 98 IP - 2 DP - 2023 Feb TI - Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival. PG - 282-289 LID - 10.1002/ajh.26778 [doi] AB - We retrospectively reviewed 72 anemic patients with myelofibrosis (MF; median age 68 years), who were JAK2 inhibitor-naïve at the time of study entry to a phase-1/2 momelotinib clinical trial. Driver mutation profile included JAK2 69%, CALR 17%, MPL 8%, and triple-negative 6%; other mutations included ASXL1 39% and SRSF2 17%. Momelotinib was administered at a median dose of 300 mg daily. Anemia response was assessed by formal criteria and documented in 44% of all patients with hemoglobin levels below the sex-adjusted reference range (n = 72), 48% of those with hemoglobin <10 g/dl (n = 54), and 46% of those who were transfusion-dependent at the time of study entry (n = 28). Anemia response was more likely with post-essential thrombocythemia MF (83% vs 37%; p = .001), lower serum ferritin (p = .003), and shorter time from diagnosis to momelotinib therapy (p = .001); the first two variables were also predictive in transfusion-dependent patients. Post-momelotinib median survival was 3.2 years; in univariate analysis, survival was superior in anemia responders (median 3.8 vs. 2.8 years; p = .14) and in the presence of type 1/like CALR mutation and inferior in the presence of age > 65 years, ASXL1/SRSF2 mutation, unfavorable karyotype, DIPSS-plus high risk, red cell transfusion need and higher serum ferritin. Multivariable analysis confirmed the favorable impact of anemia response on survival (p = .02; HR 0.5, 3/5/10-year survival; 69%/38%/25%). This survival advantage was also noted in transfusion-dependent patients (3.7 vs. 1.9 years; p = .01; HR 0.3) and appeared to be restricted to patients with an unfavorable genetic profile. The current study suggests a short-term survival benefit associated with anemia response in momelotinib-treated patients with MF. CI - © 2022 Wiley Periodicals LLC. FAU - Gangat, Naseema AU - Gangat N AUID- ORCID: 0000-0002-9104-6172 AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Begna, Kebede H AU - Begna KH AUID- ORCID: 0000-0003-2730-8593 AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Al-Kali, Aref AU - Al-Kali A AUID- ORCID: 0000-0002-0824-3715 AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Hogan, William AU - Hogan W AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Litzow, Mark AU - Litzow M AUID- ORCID: 0000-0002-9816-6302 AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Pardanani, Animesh AU - Pardanani A AUID- ORCID: 0000-0002-9084-4148 AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Tefferi, Ayalew AU - Tefferi A AUID- ORCID: 0000-0003-4605-3821 AD - Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA. LA - eng PT - Journal Article DEP - 20221115 PL - United States TA - Am J Hematol JT - American journal of hematology JID - 7610369 RN - 6O01GMS00P (N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide) RN - EC 2.7.10.2 (Janus Kinase 2) RN - 9007-73-2 (Ferritins) RN - 0 (Calreticulin) SB - IM MH - Humans MH - Aged MH - *Primary Myelofibrosis/drug therapy/genetics/diagnosis MH - Retrospective Studies MH - Mutation MH - Janus Kinase 2/genetics MH - *Anemia/drug therapy/etiology MH - Ferritins/genetics MH - Calreticulin/genetics EDAT- 2022/11/10 06:00 MHDA- 2023/01/13 06:00 CRDT- 2022/11/09 03:13 PHST- 2022/11/04 00:00 [received] PHST- 2022/11/05 00:00 [accepted] PHST- 2022/11/10 06:00 [pubmed] PHST- 2023/01/13 06:00 [medline] PHST- 2022/11/09 03:13 [entrez] AID - 10.1002/ajh.26778 [doi] PST - ppublish SO - Am J Hematol. 2023 Feb;98(2):282-289. doi: 10.1002/ajh.26778. Epub 2022 Nov 15. PMID- 36064839 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230111 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 117 IP - 1 DP - 2023 Jan TI - Guidelines for the treatment of chronic myeloid leukemia from the NCCN and ELN: differences and similarities. PG - 3-15 LID - 10.1007/s12185-022-03446-1 [doi] AB - Patients diagnosed with chronic myeloid leukemia (CML) in chronic phase can now have a life expectancy comparable to that of the general population thanks to the use of tyrosine kinase inhibitor (TKI) therapies. Although most patients with CML require lifelong TKI therapy, it is possible for some patients to achieve treatment-free remission. These spectacular results have been made possible by the development of superior treatment modalities as well as clinicians' efforts in strictly adhering to clinical guidelines such as the National Comprehensive Cancer Network (NCCN) and European Leukemia Network (ELN). CML treatment recommendations reported in these guidelines are the result of years of selecting and incorporating the most reliable evidence. In this review, we provide a synopsis of the differences and similarities that exist between the NCCN and ELN guidelines. CI - © 2022. Japanese Society of Hematology. FAU - Narlı Özdemir, Zehra AU - Narlı Özdemir Z AD - Department of Hematology, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey. FAU - Kılıçaslan, Necati Alp AU - Kılıçaslan NA AD - Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey. FAU - Yılmaz, Musa AU - Yılmaz M AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Eşkazan, Ahmet Emre AU - Eşkazan AE AUID- ORCID: 0000-0001-9568-0894 AD - Division of Hematology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Fatih, Istanbul, Turkey. emre.eskazan@iuc.edu.tr. LA - eng PT - Journal Article PT - Review DEP - 20220905 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Humans MH - *Protein Kinase Inhibitors MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/epidemiology MH - Molecular Targeted Therapy OTO - NOTNLM OT - Chronic myeloid leukemia OT - European LeukemiaNet OT - National comprehensive cancer network OT - Treatment-free remission OT - Tyrosine kinase inhibitors EDAT- 2022/09/07 06:00 MHDA- 2023/01/07 06:00 CRDT- 2022/09/06 00:09 PHST- 2022/08/17 00:00 [received] PHST- 2022/08/25 00:00 [accepted] PHST- 2022/08/25 00:00 [revised] PHST- 2022/09/07 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/09/06 00:09 [entrez] AID - 10.1007/s12185-022-03446-1 [pii] AID - 10.1007/s12185-022-03446-1 [doi] PST - ppublish SO - Int J Hematol. 2023 Jan;117(1):3-15. doi: 10.1007/s12185-022-03446-1. Epub 2022 Sep 5. PMID- 36037430 OWN - NLM STAT- MEDLINE DCOM- 20230109 LR - 20230120 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 141 IP - 1 DP - 2023 Jan 5 TI - Chronic conditions, late mortality, and health status after childhood AML: a Childhood Cancer Survivor Study report. PG - 90-101 LID - 10.1182/blood.2022016487 [doi] AB - Five-year survival following childhood acute myeloid leukemia (AML) has increased following improvements in treatment and supportive care. Long-term health outcomes are unknown. To address this, cumulative incidence of late mortality and grades 3 to 5 chronic health condition (CHC) were estimated among 5-year AML survivors diagnosed between 1970 and 1999. Survivors were compared by treatment group (hematopoietic cell transplantation [HCT], chemotherapy with cranial radiation [chemo + CRT], chemotherapy only [chemo-only]), and diagnosis decade. Self-reported health status was compared across treatments, diagnosis decade, and with siblings. Among 856 survivors (median diagnosis age, 7.1 years; median age at last follow-up, 29.4 years), 20-year late mortality cumulative incidence was highest after HCT (13.9%; 95% confidence interval [CI], 10.0%-17.8%; chemo + CRT, 7.6%; 95% CI, 2.2%-13.1%; chemo-only, 5.1%; 95% CI, 2.8%-7.4%). Cumulative incidence of mortality for HCT survivors diagnosed in the 1990s (8.5%; 95% CI, 4.1%-12.8%) was lower vs those diagnosed in the 1970s (38.9%; 95% CI, 16.4%-61.4%). Most survivors did not experience any grade 3 to 5 CHC after 20 years (HCT, 45.8%; chemo + CRT, 23.7%; chemo-only, 27.0%). Furthermore, a temporal reduction in CHC cumulative incidence was seen after HCT (1970s, 76.1%; 1990s, 38.3%; P = .02), mirroring reduced use of total body irradiation. Self-reported health status was good to excellent for 88.2% of survivors; however, this was lower than that for siblings (94.8%; P < .0001). Although HCT is associated with greater long-term morbidity and mortality than chemotherapy-based treatment, gaps have narrowed, and all treatment groups report favorable health status. CI - © 2023 by The American Society of Hematology. FAU - Turcotte, Lucie M AU - Turcotte LM AUID- ORCID: 0000-0003-4106-6172 AD - Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN. FAU - Whitton, Jillian A AU - Whitton JA AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. FAU - Leisenring, Wendy M AU - Leisenring WM AUID- ORCID: 0000-0001-7405-0906 AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. FAU - Howell, Rebecca M AU - Howell RM AD - Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Neglia, Joseph P AU - Neglia JP AUID- ORCID: 0000-0002-5525-0598 AD - Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN. FAU - Phelan, Rachel AU - Phelan R AD - Center for International Blood and Marrow Transplantation, Milwaukee, WI. AD - Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI. FAU - Oeffinger, Kevin C AU - Oeffinger KC AD - Department of Medicine, Duke University School of Medicine, Durham, NC. FAU - Ness, Kirsten K AU - Ness KK AUID- ORCID: 0000-0002-2084-1507 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN. FAU - Woods, William G AU - Woods WG AD - Aflac Cancer Center, Children's Healthcare of Atlanta/Emory University, Atlanta, GA. FAU - Kolb, E Anders AU - Kolb EA AD - Nemours Center for Cancer and Blood Disorders, Nemours Children's Health System, Wilmington, DE. FAU - Robison, Leslie L AU - Robison LL AUID- ORCID: 0000-0001-7460-8578 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN. FAU - Armstrong, Gregory T AU - Armstrong GT AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN. FAU - Chow, Eric J AU - Chow EJ AUID- ORCID: 0000-0001-7712-961X AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. LA - eng GR - K08 CA234232/CA/NCI NIH HHS/United States GR - P30 CA021765/CA/NCI NIH HHS/United States GR - U24 CA055727/CA/NCI NIH HHS/United States GR - U24 CA076518/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 SB - IM CIN - Blood. 2023 Jan 5;141(1):5-7. PMID: 36602824 MH - Humans MH - Child MH - Adult MH - *Cancer Survivors MH - Outcome Assessment, Health Care MH - *Myeloproliferative Disorders MH - Health Status MH - *Leukemia, Myeloid, Acute/therapy MH - Chronic Disease PMC - PMC9837436 COIS- Conflict-of-interest disclosure: The authors declare no competing financial interests. EDAT- 2022/08/30 06:00 MHDA- 2023/01/10 06:00 PMCR- 2024/01/05 CRDT- 2022/08/29 16:12 PHST- 2022/08/11 00:00 [accepted] PHST- 2022/03/28 00:00 [received] PHST- 2024/01/05 00:00 [pmc-release] PHST- 2022/08/30 06:00 [pubmed] PHST- 2023/01/10 06:00 [medline] PHST- 2022/08/29 16:12 [entrez] AID - 486440 [pii] AID - 10.1182/blood.2022016487 [doi] PST - ppublish SO - Blood. 2023 Jan 5;141(1):90-101. doi: 10.1182/blood.2022016487. PMID- 36031433 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230111 IS - 1465-3931 (Electronic) IS - 0031-3025 (Linking) VI - 55 IP - 1 DP - 2023 Feb TI - Novel modes of MPL activation in triple-negative myeloproliferative neoplasms. PG - 77-85 LID - S0031-3025(22)00219-7 [pii] LID - 10.1016/j.pathol.2022.05.015 [doi] AB - The identification of a somatic mutation associated with myeloid malignancy is of diagnostic importance in myeloproliferative neoplasms (MPNs). Individuals with no mutation detected in common screening tests for variants in JAK2, CALR, and MPL are described as 'triple-negative' and pose a diagnostic challenge if there is no other evidence of a clonal disorder. To identify potential drivers that might explain the clinical phenotype, we used an extended sequencing panel to characterise a cohort of 44 previously diagnosed triple-negative MPN patients for canonical mutations in JAK2, MPL and CALR at low variant allele frequency (found in 4/44 patients), less common variants in the JAK-STAT signalling pathway (12 patients), or other variants in recurrently mutated genes from myeloid malignancies (18 patients), including hotspot variants of potential clinical relevance in eight patients. In one patient with thrombocytosis we identified biallelic germline MPL variants. Neither MPL variant was activating in cell proliferation assays, and one of the variants was not expressed on the cell surface, yet co-expression of both variants led to thrombopoietin hypersensitivity. Our results highlight the clinical value of extended sequencing including germline variant analysis and illustrate the need for detailed functional assays to determine whether rare variants in JAK2 or MPL are pathogenic. CI - Copyright © 2022 Royal College of Pathologists of Australasia. All rights reserved. FAU - Samaraweera, Saumya E AU - Samaraweera SE AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia. FAU - Geukens, Tatjana AU - Geukens T AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; Department of Oncology, KU Leuven, Leuven, Belgium. FAU - Casolari, Debora A AU - Casolari DA AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia. FAU - Nguyen, Tran AU - Nguyen T AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia. FAU - Sun, Caitlyn AU - Sun C AD - Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia. FAU - Bailey, Sheree AU - Bailey S AD - UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia. FAU - Moore, Sarah AU - Moore S AD - Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia. FAU - Feng, Jinghua AU - Feng J AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; ACRF Cancer Genomics Facility, SA Pathology, Adelaide, SA, Australia. FAU - Schreiber, Andreas W AU - Schreiber AW AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; ACRF Cancer Genomics Facility, SA Pathology, Adelaide, SA, Australia; School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia. FAU - Parker, Wendy T AU - Parker WT AD - Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia. FAU - Brown, Anna L AU - Brown AL AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia. FAU - Butcher, Carolyn AU - Butcher C AD - Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Bardy, Peter G AU - Bardy PG AD - Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Osborn, Michael AU - Osborn M AD - South Australia/Northern Territory Youth Cancer Service, Royal Adelaide Hospital, Adelaide, SA, Australia; Department of Haematology and Oncology, Women's and Children's Hospital, North Adelaide, SA, Australia. FAU - Scott, Hamish S AU - Scott HS AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia; ACRF Cancer Genomics Facility, SA Pathology, Adelaide, SA, Australia. FAU - Talaulikar, Dipti AU - Talaulikar D AD - Haematology Translational Research Unit, ACT Pathology, Canberra Hospital, Canberra, ACT, Australia. FAU - Grove, Carolyn S AU - Grove CS AD - Department of Haematology, Sir Charles Gairdner Hospital and PathWest, Perth, WA, Australia. FAU - Hahn, Christopher N AU - Hahn CN AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia. FAU - D'Andrea, Richard J AU - D'Andrea RJ AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia. FAU - Ross, David M AU - Ross DM AD - Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia; Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, SA, Australia. Electronic address: david.ross@sa.gov.au. LA - eng PT - Journal Article DEP - 20220805 PL - England TA - Pathology JT - Pathology JID - 0175411 RN - 0 (Receptors, Thrombopoietin) RN - 0 (Calreticulin) RN - 143641-95-6 (MPL protein, human) SB - IM MH - Humans MH - Receptors, Thrombopoietin/genetics MH - Calreticulin/genetics/metabolism MH - *Neoplasms MH - *Myeloproliferative Disorders/diagnosis/genetics MH - Mutation OTO - NOTNLM OT - MPL activation OT - MPL variants OT - Myeloproliferative neoplasms OT - triple-negative MPN EDAT- 2022/08/29 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/08/28 22:03 PHST- 2022/02/14 00:00 [received] PHST- 2022/05/19 00:00 [revised] PHST- 2022/05/31 00:00 [accepted] PHST- 2022/08/29 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/08/28 22:03 [entrez] AID - S0031-3025(22)00219-7 [pii] AID - 10.1016/j.pathol.2022.05.015 [doi] PST - ppublish SO - Pathology. 2023 Feb;55(1):77-85. doi: 10.1016/j.pathol.2022.05.015. Epub 2022 Aug 5. PMID- 36208190 OWN - NLM STAT- MEDLINE DCOM- 20230118 LR - 20230118 IS - 1600-0609 (Electronic) IS - 0902-4441 (Linking) VI - 110 IP - 2 DP - 2023 Feb TI - Non-driver gene mutation analysis in a large cohort of polycythemia vera and essential thrombocythemia. PG - 131-136 LID - 10.1111/ejh.13882 [doi] AB - OBJECTIVES: A proportion of patients with polycythemia vera (PV) and essential thrombocythemia (ET) harbor non-driver mutations associated with poor prognosis. In this study, we analyzed the frequency of non-driver mutations in a large Japanese PV and ET cohort. Furthermore, we studied the relationship of these mutations and prognosis in Japanese patients. METHODS: We enrolled 843 Japanese patients with PV or ET. Non-driver mutations were analyzed by target resequencing using next-generation sequencing. The association of the mutations with the prognosis was estimated using multivariable logistic regression analysis and log-rank test. RESULTS: Non-driver mutations were detected in 31.1% and 24.5% patients with PV and ET, respectively. Among them, ASXL1 mutations were identified as a risk factor for leukemic/myelofibrotic transformation in PV and ET patients (hazard ratio: 4.68, p = .006). The higher-risk groups of the mutation-enhanced international prognostic system (MIPSS)-PV and MIPSS-ET incorporating non-driver mutations exhibited significantly shorter overall survival compared with the low-risk group (p < .001). CONCLUSIONS: These results implicate the importance of studying non-driver mutations for predicting the prognosis and survival of Japanese PV and ET patients. CI - © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Morishita, Soji AU - Morishita S AUID- ORCID: 0000-0003-1081-0130 AD - Laboratory for the Development of Therapies Against MPN, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - Advanced Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Hashimoto, Yoshinori AU - Hashimoto Y AUID- ORCID: 0000-0002-3374-9814 AD - Advanced Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - Department of Hematology, Tottori Prefectural Central Hospital, Tottori, Japan. FAU - Furuya, Chiho AU - Furuya C AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Edahiro, Yoko AU - Edahiro Y AUID- ORCID: 0000-0002-8386-1871 AD - Advanced Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Ochiai, Tomonori AU - Ochiai T AUID- ORCID: 0000-0001-6156-4211 AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Shirane, Shuichi AU - Shirane S AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Inano, Tadaaki AU - Inano T AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Yasuda, Hajime AU - Yasuda H AUID- ORCID: 0000-0002-2896-7737 AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Ando, Miki AU - Ando M AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Araki, Marito AU - Araki M AUID- ORCID: 0000-0002-3502-5000 AD - Laboratory for the Development of Therapies Against MPN, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - Advanced Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Komatsu, Norio AU - Komatsu N AUID- ORCID: 0000-0003-1880-9126 AD - Laboratory for the Development of Therapies Against MPN, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - Advanced Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan. AD - PharmaEssentia Japan K.K., Tokyo, Japan. LA - eng GR - Japan Society for the Promotion of Science/ GR - FUJIFILM Wako Pure Chemical Corporation/ GR - Fuso Pharmaceutical/ GR - Pfizer/ GR - PharmaEssentia/ GR - Shire International GmbH/ GR - Perseus Proteomics/ GR - Meiji Seika Pharma for Research Grant and Otsuka Pharmaceutical/ GR - Chugai Pharmaceutical/ GR - Kyowa Kirin/ GR - Takeda Pharmaceutical Company/ GR - Novartis/ GR - Sumitomo Pharma/ PT - Journal Article DEP - 20221017 PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Humans MH - *Polycythemia Vera/diagnosis/genetics MH - *Thrombocythemia, Essential/diagnosis/genetics MH - Prognosis MH - Mutation MH - *Primary Myelofibrosis MH - Janus Kinase 2/genetics OTO - NOTNLM OT - essential thrombocythemia OT - non-driver mutations OT - polycythemia vera OT - prognosis EDAT- 2022/10/09 06:00 MHDA- 2023/01/19 06:00 CRDT- 2022/10/08 08:52 PHST- 2022/10/01 00:00 [revised] PHST- 2022/08/22 00:00 [received] PHST- 2022/10/03 00:00 [accepted] PHST- 2022/10/09 06:00 [pubmed] PHST- 2023/01/19 06:00 [medline] PHST- 2022/10/08 08:52 [entrez] AID - 10.1111/ejh.13882 [doi] PST - ppublish SO - Eur J Haematol. 2023 Feb;110(2):131-136. doi: 10.1111/ejh.13882. Epub 2022 Oct 17. PMID- 36542963 OWN - NLM STAT- MEDLINE DCOM- 20230109 LR - 20230111 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 124 DP - 2023 Jan TI - Clinical characteristics and outcomes of EZH2-mutant myelodysplastic syndrome: A large single institution analysis of 1774 patients. PG - 106999 LID - S0145-2126(22)00375-7 [pii] LID - 10.1016/j.leukres.2022.106999 [doi] AB - EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p < 0.001). Patients with EZH2mut MDS had lower response rates to hypomethylating agents compared to EZH2wt MDS (26% vs. 39%; p = 0.050). Median OS of patients with EZH2mut MDS was 30.8 months, with a significantly worse OS than EZH2wt group (35.5 vs. 61.2 months, p = 0.003) in the lower-risk IPSS-R categories. Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS. CI - Copyright © 2022 Elsevier Ltd. All rights reserved. FAU - Ball, Somedeb AU - Ball S AD - Division of Hematology and Medical Oncology, University of South Florida/ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address: Somedeb.Ball@moffitt.org. FAU - Aguirre, Luis E AU - Aguirre LE AD - Division of Hematology and Medical Oncology, University of South Florida/ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Jain, Akriti G AU - Jain AG AD - Division of Hematology and Medical Oncology, University of South Florida/ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Ali, Najla Al AU - Ali NA AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Tinsley, Sara M AU - Tinsley SM AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Chan, Onyee AU - Chan O AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Kuykendall, Andrew T AU - Kuykendall AT AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Sweet, Kendra AU - Sweet K AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Lancet, Jeffrey E AU - Lancet JE AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Sallman, David A AU - Sallman DA AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Hussaini, Mohammad Omar AU - Hussaini MO AD - Department of Hematopathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Padron, Eric AU - Padron E AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Komrokji, Rami S AU - Komrokji RS AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. LA - eng PT - Journal Article DEP - 20221214 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Transcription Factors) RN - EC 2.1.1.43 (EZH2 protein, human) RN - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) SB - IM MH - Humans MH - Aged MH - Prognosis MH - Retrospective Studies MH - *Myelodysplastic Syndromes/therapy MH - *Myeloproliferative Disorders MH - Chromosome Aberrations MH - Mutation MH - Transcription Factors/genetics MH - Enhancer of Zeste Homolog 2 Protein/genetics OTO - NOTNLM OT - ASXL1 OT - Deletion 7q OT - EZH2 OT - Hypomethylating agent OT - Overall survival OT - RUNX1 COIS- Conflict of Interest: Hussaini Consultancy/Advisory Board/Speaking for Adaptive Biotechnologies, Amgen, Aptitude Health, Bluprint Oncology, Celgene, Decibio, Diaceutics, Guidepoint, Seattle Genetics, Stemline, Tegus, Janssen. Tinsley-Vance: Jazz: Consultancy, Speakers Bureau; Taiho: Consultancy; Abbvie: Honoraria; Astellas: Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy; Fresenius Kabi: Consultancy. Kuykendall: BluePrint Medicines: Honoraria, Research Funding, Speakers Bureau; Celgene/BMS: Honoraria, Research Funding, Speakers Bureau; CTI Biopharma: Honoraria; Incyte: Consultancy; Novartis: Honoraria, Speakers Bureau; PharmaEssentia: Honoraria; Prelude: Research Funding; Abbvie: Honoraria; Protagonist: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sweet: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Lancet: AbbVie: Consultancy; Millennium Pharma/Takeda: Consultancy; Daiichi Sankyo: Consultancy; BerGenBio: Consultancy; ElevateBio Management: Consultancy; Astellas: Consultancy; Agios: Consultancy; Celgene/BMS: Consultancy; Jazz: Consultancy. Sallman: Takeda: Consultancy; Agios: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intellia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Magenta: Consultancy. Padron: Blueprint: Honoraria; Taiho: Honoraria; Incyte: Research Funding; BMS: Research Funding; Stemline: Honoraria; Kura: Research Funding. Komrokji: Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; AbbVie: Consultancy; Acceleron: Consultancy; Jazz: Consultancy, Speakers Bureau; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ball, Aguirre, Jain, Ali, Chan, and Padron: No conflict of interest to declare. EDAT- 2022/12/22 06:00 MHDA- 2023/01/10 06:00 CRDT- 2022/12/21 18:11 PHST- 2022/08/06 00:00 [received] PHST- 2022/11/26 00:00 [revised] PHST- 2022/12/12 00:00 [accepted] PHST- 2022/12/22 06:00 [pubmed] PHST- 2023/01/10 06:00 [medline] PHST- 2022/12/21 18:11 [entrez] AID - S0145-2126(22)00375-7 [pii] AID - 10.1016/j.leukres.2022.106999 [doi] PST - ppublish SO - Leuk Res. 2023 Jan;124:106999. doi: 10.1016/j.leukres.2022.106999. Epub 2022 Dec 14. PMID- 36369657 OWN - NLM STAT- MEDLINE DCOM- 20230103 LR - 20230111 IS - 1469-896X (Electronic) IS - 0961-8368 (Print) IS - 0961-8368 (Linking) VI - 32 IP - 1 DP - 2023 Jan TI - Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire. PG - e4504 LID - 10.1002/pro.4504 [doi] LID - e4504 AB - Bcr-Abl, a nonreceptor tyrosine kinase, is associated with leukemias, especially chronic myeloid leukemia (CML). Deletion of Abl's N-terminal region, to which myristoyl is linked, renders the Bcr-Abl fusion oncoprotein constitutively active. The substitution of Abl's N-terminal region by Bcr enables Bcr-Abl oligomerization. Oligomerization is critical: it promotes clustering on the membrane, which is essential for potent MAPK signaling and cell proliferation. Here we decipher the Bcr-Abl specific, step-by-step oligomerization process, identify a specific packing surface, determine exactly how the process is structured and identify its key elements. Bcr's coiled coil (CC) domain at the N-terminal controls Bcr-Abl oligomerization. Crystallography validated oligomerization via Bcr-Abl dimerization between two Bcr CC domains, with tetramerization via tight packing between two binary assemblies. However, the structural principles guiding Bcr CC domain oligomerization are unknown, hindering mechanistic understanding and drugs exploiting it. Using molecular dynamics (MD) simulations, we determine that the binary complex of the Bcr CC domain serves as a basic unit in the quaternary complex providing a specific surface for dimer-dimer packing and higher-order oligomerization. We discover that the small α1-helix is the key. In the binary assembly, the helix forms interchain aromatic dimeric packing, and in the quaternary assembly, it contributes to the specific dimer-dimer packing. Our mechanism is supported by the experimental literature. It offers the key elements controlling this process which can expand the drug discovery strategy, including by Bcr CC-derived peptides, and candidate residues for small covalent drugs, toward quenching oligomerization, supplementing competitive and allosteric tyrosine kinase inhibitors. CI - © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. FAU - Liu, Yonglan AU - Liu Y AD - Cancer Innovation Laboratory, National Cancer Institute, Frederick, Maryland, USA. FAU - Zhang, Mingzhen AU - Zhang M AD - Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. FAU - Jang, Hyunbum AU - Jang H AD - Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. FAU - Nussinov, Ruth AU - Nussinov R AUID- ORCID: 0000-0002-8115-6415 AD - Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. AD - Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng GR - HHSN261201500003I/CA/NCI NIH HHS/United States GR - National Institutes of Health (NIH)/ GR - CCR/ PT - Journal Article PL - United States TA - Protein Sci JT - Protein science : a publication of the Protein Society JID - 9211750 RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) RN - 0 (Peptides) SB - IM MH - Humans MH - *Fusion Proteins, bcr-abl/genetics/chemistry MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics/metabolism MH - Cell Proliferation MH - Peptides PMC - PMC9795542 OTO - NOTNLM OT - Bcr OT - covalent inhibitors OT - fusion protein OT - molecular dynamics OT - oligomerization domain OT - peptide inhibitor COIS- The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. EDAT- 2022/11/13 06:00 MHDA- 2023/01/04 06:00 CRDT- 2022/11/12 00:52 PHST- 2022/10/31 00:00 [revised] PHST- 2022/08/30 00:00 [received] PHST- 2022/11/06 00:00 [accepted] PHST- 2022/11/13 06:00 [pubmed] PHST- 2023/01/04 06:00 [medline] PHST- 2022/11/12 00:52 [entrez] AID - PRO4504 [pii] AID - 10.1002/pro.4504 [doi] PST - ppublish SO - Protein Sci. 2023 Jan;32(1):e4504. doi: 10.1002/pro.4504. PMID- 36599841 OWN - NLM STAT- MEDLINE DCOM- 20230123 LR - 20230123 IS - 2044-5385 (Electronic) IS - 2044-5385 (Linking) VI - 13 IP - 1 DP - 2023 Jan 4 TI - Determinants of survival and retrospective comparisons of 183 clinical trial patients with myelofibrosis treated with momelotinib, ruxolitinib, fedratinib or BMS- 911543 JAK2 inhibitor. PG - 3 LID - 10.1038/s41408-022-00780-9 [doi] LID - 3 AB - Between October 2007 and July 2013, 183 Mayo Clinic patients (median age 65 years; 58% males) with high/intermediate risk myelofibrosis (MF) were enrolled in consecutive phase 1/2 JAK2 inhibitor (JAKi) clinical trials with momelotinib (n = 79), ruxolitinib (n = 50), fedratinib (n = 23) and BMS-911543 (n = 31). Using conventional criteria, the respective response rates for spleen and "transfusion-dependent anemia" were 47%, 32%, 83%, 62% and 51%, 30%, 10%, 44%, respectively, favoring momelotinib for anemia response (p = 0.02) and fedratinib for spleen response (p < 0.01). All study patients were followed to death or 2022, during which time 177 (97%) drug discontinuations, 27 (15%) leukemic transformations, and 22 (12%) allogeneic stem cell transplants (ASCT) were recorded. 5/10-year survival rate for all 183 patients was 41%/16% and not significantly different across the four drug cohorts (p = 0.33). Multivariable analysis of pre-treatment variables identified age >65 years (HR 3.5), absence of type 1/like CALR mutation (HR 2.8), baseline transfusion need (HR 2.1), and presence of ASXL1/SRSF2 mutation (HR 1.6) as risk factors for overall survival; subsequent HR-based modeling segregated three risk categories with 5/10-year survival rates of 84%/60%, 44%/14%, and 21%/5% (p < 0.01). In addition, spleen (p < 0.01) and anemia (p = 0.01) responses were independently associated with improved short-term survival while long-term survival was secured only by ASCT (5/10-year survival rate 91%/45% vs 47%/19% in non-transplanted patients; p < 0.01). The current retrospective study suggests the value of specific pre-treatment variables in identifying long-lived MF patients receiving JAKi and also confirms recent observations on the favorable impact of treatment response on short-term and of ASCT on long-term survival. CI - © 2022. The Author(s). FAU - Gangat, Naseema AU - Gangat N AUID- ORCID: 0000-0002-9104-6172 AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Begna, Kebede H AU - Begna KH AUID- ORCID: 0000-0003-2730-8593 AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Al-Kali, Aref AU - Al-Kali A AUID- ORCID: 0000-0002-0824-3715 AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Hogan, William AU - Hogan W AUID- ORCID: 0000-0002-5841-4105 AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Litzow, Mark AU - Litzow M AUID- ORCID: 0000-0002-9816-6302 AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Pardanani, Animesh AU - Pardanani A AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Tefferi, Ayalew AU - Tefferi A AUID- ORCID: 0000-0003-4605-3821 AD - Division of Hematology, Mayo Clinic, Rochester, MN, USA. tefferi.ayalew@mayo.edu. LA - eng PT - Journal Article DEP - 20230104 PL - United States TA - Blood Cancer J JT - Blood cancer journal JID - 101568469 RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Janus Kinase 2) RN - 0 (Janus Kinase Inhibitors) RN - 0 (N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo(4,5-d)pyrrolo(2,3b)pyridine-7-carboxamide) RN - 6O01GMS00P (N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide) RN - 82S8X8XX8H (ruxolitinib) RN - 0 (Sulfonamides) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - *Anemia/drug therapy MH - Janus Kinase 2/genetics/metabolism MH - *Janus Kinase Inhibitors/therapeutic use MH - *Primary Myelofibrosis/drug therapy/genetics/mortality MH - Retrospective Studies MH - Sulfonamides/therapeutic use MH - Survival Rate PMC - PMC9813003 COIS- The authors declare no competing interests. EDAT- 2023/01/05 06:00 MHDA- 2023/01/07 06:00 CRDT- 2023/01/04 23:13 PHST- 2022/11/14 00:00 [received] PHST- 2022/12/19 00:00 [accepted] PHST- 2022/12/15 00:00 [revised] PHST- 2023/01/04 23:13 [entrez] PHST- 2023/01/05 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] AID - 10.1038/s41408-022-00780-9 [pii] AID - 780 [pii] AID - 10.1038/s41408-022-00780-9 [doi] PST - epublish SO - Blood Cancer J. 2023 Jan 4;13(1):3. doi: 10.1038/s41408-022-00780-9. PMID- 36641455 OWN - NLM STAT- MEDLINE DCOM- 20230118 LR - 20230118 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 23 IP - 1 DP - 2023 Jan 14 TI - Trends in overall mortality among US veterans with primary myelofibrosis. PG - 48 LID - 10.1186/s12885-022-10495-6 [doi] LID - 48 AB - BACKGROUND: Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment. METHODS: This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007-12/31/2010) and post-ruxolitinib approval (01/01/2015-09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin < 10 g/dL, and white blood cell count > 25 × 10(9)/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression. RESULTS: The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2-2.6] years vs not reached [3.4-not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37-0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors. CONCLUSIONS: Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period. CI - © 2023. The Author(s). FAU - Tashi, Tsewang AU - Tashi T AD - Division of Hematology & Hematologic Malignancies, Huntsman Cancer Institute, University of Utah & SLC VAMC, Salt Lake City, UT, 84112, USA. tsewang.tashi@utah.edu. FAU - Yu, Jingbo AU - Yu J AD - Incyte Corporation, Wilmington, DE, USA. FAU - Pandya, Shivani AU - Pandya S AD - STATinMED LLC, Dallas, TX, USA. FAU - Dieyi, Christopher AU - Dieyi C AD - STATinMED LLC, Dallas, TX, USA. AD - Baylor College of Medicine, Houston, TX, USA. FAU - Scherber, Robyn AU - Scherber R AD - Incyte Corporation, Wilmington, DE, USA. AD - UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, USA. FAU - Parasuraman, Shreekant AU - Parasuraman S AD - Incyte Corporation, Wilmington, DE, USA. LA - eng PT - Journal Article DEP - 20230114 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Nitriles) RN - 0 (Pyrazoles) RN - 82S8X8XX8H (ruxolitinib) SB - IM MH - Adult MH - Humans MH - Nitriles MH - *Primary Myelofibrosis/diagnosis/drug therapy/mortality MH - Pyrazoles/pharmacology MH - Retrospective Studies MH - *Veterans MH - United States PMC - PMC9840363 OTO - NOTNLM OT - Mortality OT - Myelofibrosis OT - Ruxolitinib OT - Veterans COIS- TT reports no conflict of interest. JY, RS, and SParasuraman are employees of Incyte Corporation. CD is an employee of STATinMED LLC, which is a paid consultant of Incyte Corporation. SPandya was an employee of STATinMED LLC at the time of the analysis. This study was funded by Incyte Corporation. EDAT- 2023/01/15 06:00 MHDA- 2023/01/18 06:00 CRDT- 2023/01/14 23:14 PHST- 2022/02/04 00:00 [received] PHST- 2022/12/29 00:00 [accepted] PHST- 2023/01/14 23:14 [entrez] PHST- 2023/01/15 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] AID - 10.1186/s12885-022-10495-6 [pii] AID - 10495 [pii] AID - 10.1186/s12885-022-10495-6 [doi] PST - epublish SO - BMC Cancer. 2023 Jan 14;23(1):48. doi: 10.1186/s12885-022-10495-6. PMID- 36629680 OWN - NLM STAT- MEDLINE DCOM- 20230113 LR - 20230113 IS - 2317-6385 (Electronic) IS - 1679-4508 (Print) IS - 1679-4508 (Linking) VI - 21 DP - 2023 TI - Molecular profile of patients with myelofibrosis: a 10-year experience. PG - eAO0100 LID - S1679-45082023000100201 [pii] LID - 10.31744/einstein_journal/2023AO0100 [doi] LID - eAO0100 AB - OBJECTIVE: To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. METHODS: Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. RESULTS: A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). CONCLUSION: The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important. FAU - Dias, Lara Faria Souza AU - Dias LFS AUID- ORCID: 0000-0002-8350-5121 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Pereira, Carolina Leme de Moura AU - Pereira CLM AUID- ORCID: 0000-0001-8209-8010 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Centurião, Newton de Freitas AU - Centurião NF AUID- ORCID: 0000-0001-9311-9980 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Nascimento, Jade Zezzi Martins do AU - Nascimento JZMD AUID- ORCID: 0000-0002-6604-5362 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Ribeiro, Andreza Alice Feitosa AU - Ribeiro AAF AUID- ORCID: 0000-0002-0017-8488 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Hamerschlak, Nelson AU - Hamerschlak N AUID- ORCID: 0000-0002-5140-5310 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Marques, Carolina Perrone AU - Marques CP AUID- ORCID: 0000-0002-1048-8068 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Lima, Ana Carolina Vieira de AU - Lima ACV AUID- ORCID: 0000-0002-2751-4314 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Costa, Luana Nóbrega da AU - Costa LND AUID- ORCID: 0000-0001-6801-9873 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Silva, Anderson Felipe da AU - Silva AFD AUID- ORCID: 0000-0002-7002-7204 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Lima, Viviane de Jesus Torres AU - Lima VJT AUID- ORCID: 0000-0002-6209-3519 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Kerbauy, Mariana Nassif AU - Kerbauy MN AUID- ORCID: 0000-0002-4441-9212 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Kerbauy, Lucila Nassif AU - Kerbauy LN AUID- ORCID: 0000-0003-4864-9098 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Arcuri, Leonardo Javier AU - Arcuri LJ AUID- ORCID: 0000-0002-9673-1945 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Campregher, Paulo Vidal AU - Campregher PV AUID- ORCID: 0000-0001-6005-405X AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Rocha, Juliana Dall Agnol da AU - Rocha JDAD AUID- ORCID: 0000-0002-2926-2384 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Datoguia, Tarcila Santos AU - Datoguia TS AUID- ORCID: 0000-0002-0718-2391 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. FAU - Santos, Fabio Pires de Souza AU - Santos FPS AUID- ORCID: 0000-0001-8573-9493 AD - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. LA - eng PT - Journal Article DEP - 20230106 PL - Brazil TA - Einstein (Sao Paulo) JT - Einstein (Sao Paulo, Brazil) JID - 101281800 SB - IM MH - Humans MH - *Primary Myelofibrosis/genetics/diagnosis/therapy MH - Retrospective Studies MH - Mutation MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - Prognosis PMC - PMC9785572 COIS- Conflict of interest: none. EDAT- 2023/01/12 06:00 MHDA- 2023/01/14 06:00 CRDT- 2023/01/11 10:08 PHST- 2022/03/21 00:00 [received] PHST- 2022/07/20 00:00 [accepted] PHST- 2023/01/11 10:08 [entrez] PHST- 2023/01/12 06:00 [pubmed] PHST- 2023/01/14 06:00 [medline] AID - S1679-45082023000100201 [pii] AID - 10.31744/einstein_journal/2023AO0100 [doi] PST - epublish SO - Einstein (Sao Paulo). 2023 Jan 6;21:eAO0100. doi: 10.31744/einstein_journal/2023AO0100. eCollection 2023. PMID- 36644935 OWN - NLM STAT- MEDLINE DCOM- 20230117 LR - 20230120 IS - 1365-2060 (Electronic) IS - 0785-3890 (Print) IS - 0785-3890 (Linking) VI - 55 IP - 1 DP - 2023 Dec TI - Efficacy and safety of combination therapies vs monotherapy of hypomethylating agents in accelerated or blast phase of Philadelphia negative myeloproliferative neoplasms: a systematic review and meta-analysis. PG - 348-360 LID - 10.1080/07853890.2022.2164611 [doi] AB - BACKGROUND: There is a lack of evidence regarding whether combination therapy of hypomethylating agents (HMAs) has better outcomes than HMA monotherapy in patients with Philadelphia chromosome-negative accelerated or blast phase myeloproliferative neoplasms (MPN-AP/BP). MATERIALS AND METHODS: Pubmed, Embase, Web of Science and Cochrane library databases were searched for studies from inception of each database until 31 December 2021. Data extraction and synthesis were conducted following the PRISMA reporting guideline. RESULTS: It was found that HMAs plus venetoclax therapy yielded a higher CR/CRi rate than HMAs alone [36% vs 19%, p = .0204] and a higher CR rate than HMAs plus ruxolitinib [22% vs 8%, p = .0313]. HMAs plus ruxolitinib combination showed a higher ORR than HMA monotherapy [45% vs 30%, p = .0395], but there was no improvement in CR/CRi. The one-year and two-year OS rate for patients treated with HMAs plus venetoclx/ruxolitinib demonstrated a trend towards prolonged survival than HMAs alone [HMAs plus venetoclax: 24% vs 11%, p = .1295 and 12% vs 3%, p = .2357; HMAs plus ruxolitinib: 25% vs 11%, p = .0774 and 33% vs 3%, p = .051]. CONCLUSION: It was confirmed that HMA in combination with venetoclax is an effective and well-tolerated option in MPN-AP/BP patients in pre- as well as post-haematopoietic stem cell transplantation settings. HMA plus ruxolitinib therapy was revealed to be effective in patients with MPN-AP.Key MessagesCombination therapy with HMAs and venetoclax/ruxolitinib was associated with improved outcomes than HMAs alone in MPN-AP/BP patients.Further large-scale randomized controlled trials are needed to confirm regarding to the optimal treatment for this patient population. FAU - Chen, Jia AU - Chen J AUID- ORCID: 0000-0002-7096-1056 AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. AD - Tianjin Institutes of Health Science, Tianjin, China. AD - MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Wang, Kefei AU - Wang K AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. AD - Tianjin Institutes of Health Science, Tianjin, China. FAU - Xiao, Zhijian AU - Xiao Z AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. AD - Tianjin Institutes of Health Science, Tianjin, China. AD - MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Xu, Zefeng AU - Xu Z AD - State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. AD - Tianjin Institutes of Health Science, Tianjin, China. AD - MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review PL - England TA - Ann Med JT - Annals of medicine JID - 8906388 RN - N54AIC43PW (venetoclax) RN - 82S8X8XX8H (ruxolitinib) RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) SB - IM MH - Humans MH - Treatment Outcome MH - *Blast Crisis/chemically induced MH - *Bridged Bicyclo Compounds, Heterocyclic/therapeutic use/adverse effects PMC - PMC9848335 OTO - NOTNLM OT - Myeloproliferative neoplasms OT - accelerated/blast phase OT - hypomethylating agents OT - ruxolitinib OT - venetoclax COIS- No potential conflict of interest was reported by the author(s). EDAT- 2023/01/17 06:00 MHDA- 2023/01/18 06:00 CRDT- 2023/01/16 04:43 PHST- 2023/01/16 04:43 [entrez] PHST- 2023/01/17 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] AID - 2164611 [pii] AID - 10.1080/07853890.2022.2164611 [doi] PST - ppublish SO - Ann Med. 2023 Dec;55(1):348-360. doi: 10.1080/07853890.2022.2164611. PMID- 36197958 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230117 IS - 1535-2900 (Electronic) IS - 1079-2082 (Linking) VI - 80 IP - 2 DP - 2023 Jan 5 TI - Asciminib (Scemblix): A third-line treatment option for chronic myeloid leukemia in chronic phase with or without T315I mutation. PG - 36-43 LID - 10.1093/ajhp/zxac286 [doi] AB - PURPOSE: To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of asciminib, an oral tyrosine kinase inhibitor (TKI) used as a third-line treatment option for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase. SUMMARY: CML is a rare cancer caused by a chromosomal translocation that forms a fusion of the BCR and ABL1 genes on chromosomes 22 and 9. Until recently, patients for whom first-line treatment options failed were treated with TKIs that bind to the adenosine triphosphate-binding site on BCR-ABL1. However, because of similar mechanisms of action, there continues to be an unmet need in patients for whom at least 2 TKIs have failed or those with a T315I mutation unable to tolerate ponatinib. In October 2021, the Food and Drug Administration approved asciminib (Scemblix), the first TKI specifically targeting the ABL1 myristoyl pocket (STAMP) via allosteric binding, as a third-line option for patients with chronic-phase (CP)-CML. Asciminib received accelerated approval due to meeting its primary endpoint at week 24, demonstrating a major molecular response rate of 25.5% for patients on asciminib compared to 13.2% for those receiving bosutinib. In addition, patients on asciminib achieved a higher rate of complete cytogenetic response at 40.8% compared to a rate of 24.2% for bosutinib. Clinicians prescribing asciminib should monitor for increased levels of pancreatic enzymes, hypertension, cardiovascular toxicity including ischemic and thromboembolic conditions, and decreased numbers of neutrophils and platelets, as these may require treatment interruption, dose reduction, or treatment discontinuation. CONCLUSION: Asciminib is a unique targeted TKI that provides clinicians with an additional third-line and beyond treatment option for adults with CP-CML regardless of mutation status as well as a second TKI treatment option for patients harboring a T315I mutation. CI - © American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Monestime, Shanada AU - Monestime S AD - Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA. FAU - Al Sagheer, Tiba AU - Al Sagheer T AD - Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA. FAU - Tadros, Monica AU - Tadros M AD - Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA. LA - eng PT - Journal Article PL - England TA - Am J Health Syst Pharm JT - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JID - 9503023 RN - 5018V4AEZ0 (bosutinib) RN - 0 (asciminib) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Antineoplastic Agents) SB - IM MH - Adult MH - Humans MH - Drug Resistance, Neoplasm/genetics MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics MH - Fusion Proteins, bcr-abl/genetics/metabolism MH - Protein Kinase Inhibitors/adverse effects MH - Mutation MH - *Antineoplastic Agents/adverse effects OTO - NOTNLM OT - Philadelphia chromosome positive OT - T315I mutation OT - asciminib OT - chronic myeloid leukemia OT - chronic phase OT - targeted therapy EDAT- 2022/10/06 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/10/05 14:04 PHST- 2022/10/06 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/10/05 14:04 [entrez] AID - 6748956 [pii] AID - 10.1093/ajhp/zxac286 [doi] PST - ppublish SO - Am J Health Syst Pharm. 2023 Jan 5;80(2):36-43. doi: 10.1093/ajhp/zxac286. PMID- 36563650 OWN - NLM STAT- MEDLINE DCOM- 20230109 LR - 20230111 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 124 DP - 2023 Jan TI - Molecular genetic characterization of Philadelphia chromosome-positive acute myeloid leukemia. PG - 107002 LID - S0145-2126(22)00378-2 [pii] LID - 10.1016/j.leukres.2022.107002 [doi] AB - BACKGROUND: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a provisional disease entity in the 2016 WHO classification, while its genetic profile of Ph+ AML remains poorly defined. In addition, the differentiating features of Ph+ AML and chronic myeloid leukemia in myeloid blast crisis (CML-MBC) remain controversial. METHODS: We conducted a retrospective study of 15 Ph+ AML patients to compare their clinical and laboratory profiles with 27 CML-MBC patients. RESULTS: Compared to CML-MBC, Ph+ AML patients presented with significantly higher peripheral WBC count and bone marrow blast percentage. The immunophenotypic profiles were largely similar between Ph+ AML and CML-MBC, except for CD4 expression, which was significantly enriched in CML-MBC. Ph+ AML patients less frequently harboured co-occurring additional cytogenetic abnormalities (ACA) compared to CML-MBC, and trisomy 19 (23%) and IDH1/2 (46%) were the most common ACA and mutated genes in Ph+ AML, respectively. Overall survival (OS) did not significantly differ between Ph+ AML and CML-MBC. Ph+ AML without CML-like features appeared to have a better outcome compared to Ph+ AML with CML-like features; ACA in Ph+ AML may confer an even worse prognosis. CONCLUSIONS: Our results indicate that patients with Ph+ AML share similar genetic profiles and clinical outcomes with those with CML-MBC, thus should be classified as a high-risk entity. CI - Copyright © 2022 Elsevier Ltd. All rights reserved. FAU - Zhou, Qianghua AU - Zhou Q AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Haematology, University Health Network, Toronto, Ontario, Canada. FAU - Zhao, Davidson AU - Zhao D AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Eladl, Entsar AU - Eladl E AD - Department of Laboratory Haematology, University Health Network, Toronto, Ontario, Canada; Pathology Department, Mansoura University, Egypt. FAU - Capo-Chichi, Jose-Mario AU - Capo-Chichi JM AD - Clinical Laboratory Genetics, Genome Diagnostics Laboratory Medicine Program, University of Toronto, Toronto, Ontario, Canada. FAU - Kim, Dennis Dong Hwan AU - Kim DDH AD - Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. FAU - Chang, Hong AU - Chang H AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Haematology, University Health Network, Toronto, Ontario, Canada. Electronic address: hong.chang@uhn.ca. LA - eng PT - Journal Article DEP - 20221216 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 SB - IM MH - Humans MH - Philadelphia Chromosome MH - Retrospective Studies MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics MH - *Leukemia, Myeloid, Acute/genetics MH - Molecular Biology OTO - NOTNLM OT - Clinical outcomes OT - Molecular cytogenetics OT - NGS OT - Ph+ AML COIS- Conflict of interest The authors declare no conflict of interest. EDAT- 2022/12/24 06:00 MHDA- 2023/01/10 06:00 CRDT- 2022/12/23 18:25 PHST- 2022/11/06 00:00 [received] PHST- 2022/12/06 00:00 [revised] PHST- 2022/12/14 00:00 [accepted] PHST- 2022/12/24 06:00 [pubmed] PHST- 2023/01/10 06:00 [medline] PHST- 2022/12/23 18:25 [entrez] AID - S0145-2126(22)00378-2 [pii] AID - 10.1016/j.leukres.2022.107002 [doi] PST - ppublish SO - Leuk Res. 2023 Jan;124:107002. doi: 10.1016/j.leukres.2022.107002. Epub 2022 Dec 16. PMID- 36288760 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230111 IS - 2666-6367 (Electronic) IS - 2666-6367 (Linking) VI - 29 IP - 1 DP - 2023 Jan TI - Haploidentical Hematopoietic Cell Transplantation for Myelofibrosis in the Ruxolitinib Era. PG - 49.e1-49.e7 LID - S2666-6367(22)01712-2 [pii] LID - 10.1016/j.jtct.2022.10.015 [doi] AB - Haploidentical stem cell transplantation is a viable strategy in the absence of an HLA-identical donor, but in myelofibrosis (MF), concerns may rise due to the risk of graft failure. Considering that engraftment is a major issue in MF, we sought to highlight its impact on survival outcomes. In addition, we explored the impact of pretransplantation ruxolitinib administration as an independent variable on outcomes. Here we report the results of a retrospective, monocentric experience with T cell-replete haploidentical bone marrow transplantation with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis in 51 consecutive MF-affected patients. The median duration of follow-up was 47 months. All 51 patients received a double-alkylating conditioning regimen, and 21 patients (41%) received pretransplantation ruxolitinib. Thirty-seven of 49 evaluable patients (76%) achieved full donor chimerism with neutrophil engraftment, 8 of 49 (16%) experienced graft rejection, and 4 of 49 (8%) had primary poor graft function. Splenectomy was more frequent among patients who engrafted (P = .06). Graft rejection was the sole factor negatively impacting overall survival (hazard ratio [HR], 4.19; 95% confidence interval [CI], 1.37 to 12.80; P = .01) and the major determinant for nonrelapse mortality (HR, 10.31; 95% CI, 2.54 to 41.82; P = .001). The 24-month incidence of relapse was 19% and was negatively impacted by splenectomy (HR, 5.84; 95% CI, 1.28 to 26.72; P = .02). The cumulative incidence of grade II-IV acute GVHD was 27% (95% CI, 20% to 33%), and that of grade III-IV acute GVHD was 8% (95% CI, 4% to 12%). The 24-month cumulative incidence of all-grade chronic GVHD was 28% (95% CI, 21% to 35%). Our data show that T cell-replete haploidentical bone marrow transplantation following double-alkylating conditioning in patients with MF is associated with favorable rates of GVHD and an acceptable relapse risk; nevertheless, rejection is not negligible and is associated with significant mortality. Splenectomy, which favors engraftment, is predictive of a higher risk of relapse. CI - Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Gambella, Massimiliano AU - Gambella M AD - Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: massimiliano.gambella@hsanmartino.it. FAU - Bregante, Stefania AU - Bregante S AD - Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Raiola, Anna Maria AU - Raiola AM AD - Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Varaldo, Riccardo AU - Varaldo R AD - Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Ghiso, Anna AU - Ghiso A AD - Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Schiavetti, Irene AU - Schiavetti I AD - Department of Health Sciences, University of Genoa, Genoa, Italy. FAU - Carmisciano, Luca AU - Carmisciano L AD - Department of Health Sciences, University of Genoa, Genoa, Italy. FAU - Bacigalupo, Andrea AU - Bacigalupo A AD - Department of Radiological and Hematological Sciences, Università Cattolica del Sacro Cuore, Rome, Italy. FAU - Angelucci, Emanuele AU - Angelucci E AD - Department of Hematology and Cellular Therapy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. LA - eng PT - Journal Article DEP - 20221023 PL - United States TA - Transplant Cell Ther JT - Transplantation and cellular therapy JID - 101774629 RN - 82S8X8XX8H (ruxolitinib) SB - IM MH - Humans MH - *Primary Myelofibrosis/therapy/complications MH - Retrospective Studies MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - *Graft vs Host Disease/prevention & control/drug therapy MH - Chronic Disease MH - Recurrence OTO - NOTNLM OT - Bone marrow source OT - Graft failure OT - Haploidentical OT - Myelofibrosis COIS- Conflict of interest statement: There are no conflicts of interest to report Authorship statement: M.G. and S.B. contributed equally to this work. EDAT- 2022/10/27 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/10/26 19:22 PHST- 2022/08/31 00:00 [received] PHST- 2022/10/17 00:00 [revised] PHST- 2022/10/19 00:00 [accepted] PHST- 2022/10/27 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/10/26 19:22 [entrez] AID - S2666-6367(22)01712-2 [pii] AID - 10.1016/j.jtct.2022.10.015 [doi] PST - ppublish SO - Transplant Cell Ther. 2023 Jan;29(1):49.e1-49.e7. doi: 10.1016/j.jtct.2022.10.015. Epub 2022 Oct 23. PMID- 36214090 OWN - NLM STAT- MEDLINE DCOM- 20230113 LR - 20230113 IS - 1365-2141 (Electronic) IS - 0007-1048 (Linking) VI - 200 IP - 2 DP - 2023 Jan TI - Dasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study). PG - 175-186 LID - 10.1111/bjh.18486 [doi] AB - Superior rates of deep molecular response (DMR) have been reported with the combination of tyrosine kinase inhibitors and pegylated-interferon-alpha (Peg-IFN) in patients with newly diagnosed chronic phase-chronic myeloid leukaemia (CP-CML). In this setting, this study investigated the efficacy and safety of dasatinib combined to Peg-IFN-α2b (Dasa-PegIFN, NCT01872442). A total of 79 patients (age ≤65 years) started dasatinib; 61 were eligible for Peg-IFNα-2b add-on therapy at month 3 for a maximum 21-months duration. Dasatinib was continued thereafter. The primary endpoint was the cumulative rate of molecular response 4.5 log (MR(4.5) ) by 12 months. The results are reported for the 5-year duration of the study. Grade 3 neutropenia was frequent with the combination but did not induce severe infection (one of grade 3). Other adverse events were generally low grade (4% of grade 3-4) and expected. Seventy-nine per cent and 61% of patients continued the Peg-IFN until months 12 and 24, respectively. Overall, at these time points, MR(4.5) rates were 25% and 38%, respectively. Thereafter, 32% and 46% of patients achieved a sustained (≥2 years) MR(4.5) or MR(4) , respectively. This work established the feasibility and high rates of achievement of early and sustained DMR (a prerequisite for treatment-free-remission) with dasatinib and Peg-IFNα-2b combination as initial therapy. CI - © 2022 British Society for Haematology and John Wiley & Sons Ltd. FAU - Roy, Lydia AU - Roy L AUID- ORCID: 0000-0002-1833-9673 AD - Hôpital Universitaire Henri Mondor, APHP, Faculté de Santé, UPEC, Service d'Hématologie Clinique, Créteil, France. FAU - Chomel, Jean-Claude AU - Chomel JC AUID- ORCID: 0000-0001-9227-1104 AD - CHU de Poitiers, Service de Cancérologie Biologique, Poitiers, France. FAU - Guilhot, Joëlle AU - Guilhot J AD - INSERM CIC 1402, CHU Poitiers, Poitiers, France. FAU - Guerci-Bresler, Agnès AU - Guerci-Bresler A AD - CHRU Brabois Vandœuvre-lès-Nancy, Service d'Hématologie Clinique, Nancy, France. FAU - Escoffre-Barbe, Martine AU - Escoffre-Barbe M AD - CHU Pontchaillou, Service d'Hématologie Clinique, Rennes, France. FAU - Giraudier, Stéphane AU - Giraudier S AD - Hôpital Saint-Louis, APHP et INSERM Université de Paris, Service de biologie cellulaire, Paris, France. FAU - Charbonnier, Aude AU - Charbonnier A AD - Institut Paoli-Calmettes, Service d'Hématologie Clinique, Marseille, France. FAU - Dubruille, Viviane AU - Dubruille V AD - CHU Hôtel Dieu, Service d'Hématologie Clinique, Nantes, France. FAU - Huguet, Françoise AU - Huguet F AD - Service d'Hématologie Clinique, CHU Toulouse, I.U.C.T.O, Toulouse, France. FAU - Johnson-Ansah, Hyacinthe AU - Johnson-Ansah H AD - CHU Caen, Service d'Hématologie Clinique, Caen, France. FAU - Lenain, Pascal AU - Lenain P AD - Centre Henri Becquerel, Service d'Hématologie Clinique, Rouen, France. FAU - Ame, Shanti AU - Ame S AD - CHU Strasbourg, Service d'Hématologie Clinique, Strasbourg, France. FAU - Etienne, Gabriel AU - Etienne G AUID- ORCID: 0000-0001-7600-4954 AD - Institut Bergonié, Service d'Hématologie Clinique, Bordeaux, France. FAU - Nicolini, Franck E AU - Nicolini FE AUID- ORCID: 0000-0002-3192-4199 AD - Centre Léon Bérard, Service d'Hématologie Clinique & INSERM U1052 CRC, Lyon, France. FAU - Rea, Delphine AU - Rea D AUID- ORCID: 0000-0001-5379-7461 AD - Hôpital St Louis, APHP, Service d'Hématologie Clinique, Paris, France. FAU - Cony-Makhoul, Pascale AU - Cony-Makhoul P AD - CH Annecy-Genevois, Service d'Hématologie, Pringy, France. FAU - Courby, Stéphane AU - Courby S AD - CHU Grenoble Service d'Hématologie Clinique, Grenoble, France. FAU - Ianotto, Jean-Christophe AU - Ianotto JC AD - Hôpital Morvan, CHU Brest, Service d'Hématologie Clinique, Brest, France. FAU - Legros, Laurence AU - Legros L AD - Hôpital Paul Brousse, AP-HP, Service d'Hématologie Clinique, INSERM UMRS-MD1197, Villejuif, France. FAU - Machet, Antoine AU - Machet A AD - Hôpital Bretonneau, CHRU Tours Service d'Hématologie Clinique, Tours, France. FAU - Coiteux, Valérie AU - Coiteux V AD - Hôpital Claude Huriez, CHRU Lille Service d'Hématologie Clinique, Lille, France. FAU - Hermet, Eric AU - Hermet E AD - CHU d'Estaing, Clermont-Ferrand, Service d'Hématologie Clinique, Clermont-Ferrand, France. FAU - Cayssials, Emilie AU - Cayssials E AUID- ORCID: 0000-0003-1654-5948 AD - INSERM CIC 1402, CHU Poitiers, Poitiers, France. AD - CHU de Poitiers, Service d'Hématologie Clinique, Poitiers, France. FAU - Bouchet, Stéphane AU - Bouchet S AD - Hôpital Pellegrin, CHU Bordeaux, Laboratoire de pharmacologie, Bordeaux, France. FAU - Mahon, Francois-Xavier AU - Mahon FX AD - Institut Bergonié, Service d'Hématologie Clinique, Bordeaux, France. FAU - Rousselot, Philippe AU - Rousselot P AUID- ORCID: 0000-0003-3238-4494 AD - Centre Hospitalier de Versailles, Université Paris Saclay UMR 1184, Service d'Hématologie Clinique, Le Chesnay, France. FAU - Guilhot, François AU - Guilhot F AD - INSERM CIC 1402, CHU Poitiers, Poitiers, France. CN - French CML Group (FiLMC) AD - French CML group (Fi-LMC), Centre Léon Bérard, Lyon, France. LA - eng GR - Bristol-Myers Squibb/ GR - Merck/ PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20221010 PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - RBZ1571X5H (Dasatinib) RN - G8RGG88B68 (peginterferon alfa-2b) RN - Z0105S98AO (diazobenzenesulfonic acid) RN - 0 (Interferon-alpha) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Humans MH - Aged MH - Dasatinib/adverse effects MH - *Interferon-alpha/adverse effects MH - *Leukemia, Myeloid, Chronic-Phase/drug therapy MH - Polyethylene Glycols/adverse effects MH - Treatment Outcome OTO - NOTNLM OT - chronic myeloid leukaemia OT - clinical trial OT - deep molecular response OT - pegylated-interferon OT - tyrosine kinase inhibitor EDAT- 2022/10/11 06:00 MHDA- 2023/01/14 06:00 CRDT- 2022/10/10 04:45 PHST- 2022/09/04 00:00 [revised] PHST- 2022/05/13 00:00 [received] PHST- 2022/09/16 00:00 [accepted] PHST- 2022/10/11 06:00 [pubmed] PHST- 2023/01/14 06:00 [medline] PHST- 2022/10/10 04:45 [entrez] AID - 10.1111/bjh.18486 [doi] PST - ppublish SO - Br J Haematol. 2023 Jan;200(2):175-186. doi: 10.1111/bjh.18486. Epub 2022 Oct 10. PMID- 36478132 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230111 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 27 IP - 1 DP - 2023 Jan TI - FUBP3 regulates chronic myeloid leukaemia progression through PRC2 complex regulated PAK1-ERK signalling. PG - 15-29 LID - 10.1111/jcmm.17584 [doi] AB - The development of resistance and heterogeneity in differential response towards tyrosine kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) treatment has led to the exploration of factors independent of the Philadelphia chromosome. Among these are the association of deletions of genes on derivative (der) 9 chromosome with adverse outcomes in CML patients. However, the functional role of genes near the breakpoint on der (9) in CML prognosis and progression remains largely unexplored. Copy number variation and mRNA expression were evaluated for five genes located near the breakpoint on der (9). Our data showed a significant association between microdeletions of the FUBP3 gene and its reduced expression with poor prognostic markers and adverse response outcomes in CML patients. Further investigation using K562 cells showed that the decrease in FUBP3 protein was associated with an increase in proliferation and survival due to activation of the MAPK-ERK pathway. We have established a novel direct interaction of FUBP3 protein and PRC2 complex in the regulation of ERK signalling via PAK1. Our findings demonstrate the role of the FUBP3 gene located on der (9) in poor response and progression in CML with the identification of additional druggable targets such as PAK1 in improving response outcomes in CML patients. CI - © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Sharma, Mugdha AU - Sharma M AUID- ORCID: 0000-0003-3651-0574 AD - Department of Medicine, St. John's Medical College and Hospital, Bengaluru, India. AD - St. John's National Academy of Health Sciences, Bengaluru, India. FAU - Anandram, Seetharam AU - Anandram S AD - St. John's National Academy of Health Sciences, Bengaluru, India. AD - Department of Clinical Hematology, St. John's Medical College and Hospital, Bengaluru, India. FAU - Ross, Cecil AU - Ross C AUID- ORCID: 0000-0002-4697-3399 AD - St. John's National Academy of Health Sciences, Bengaluru, India. AD - Department of Clinical Hematology, St. John's Medical College and Hospital, Bengaluru, India. FAU - Srivastava, Sweta AU - Srivastava S AUID- ORCID: 0000-0001-6063-0811 AD - St. John's National Academy of Health Sciences, Bengaluru, India. AD - Department of Transfusion Medicine and Immunohematology, St. John's Medical College and Hospital, Bengaluru, India. LA - eng GR - EMR/2016/003618/Science and Engineering Research Board/ PT - Journal Article DEP - 20221207 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (DNA-Binding Proteins) RN - 0 (FUBP3 protein, human) RN - EC 2.7.11.1 (p21-Activated Kinases) RN - EC 2.7.11.1 (PAK1 protein, human) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Transcription Factors) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Humans MH - *DNA Copy Number Variations MH - DNA-Binding Proteins/genetics MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics MH - p21-Activated Kinases/genetics MH - Philadelphia Chromosome MH - Protein Kinase Inhibitors/pharmacology MH - Signal Transduction MH - Transcription Factors/genetics MH - Extracellular Signal-Regulated MAP Kinases/metabolism PMC - PMC9806296 OTO - NOTNLM OT - CML OT - ERK OT - FUBP3 OT - PAK1 OT - PRC2 OT - Sokal OT - TKI OT - derivative chromosome 9 OT - fibrosis COIS- The authors declare that they have no competing interests. EDAT- 2022/12/09 06:00 MHDA- 2023/01/04 06:00 CRDT- 2022/12/08 12:38 PHST- 2022/09/08 00:00 [revised] PHST- 2022/03/09 00:00 [received] PHST- 2022/09/17 00:00 [accepted] PHST- 2022/12/09 06:00 [pubmed] PHST- 2023/01/04 06:00 [medline] PHST- 2022/12/08 12:38 [entrez] AID - JCMM17584 [pii] AID - 10.1111/jcmm.17584 [doi] PST - ppublish SO - J Cell Mol Med. 2023 Jan;27(1):15-29. doi: 10.1111/jcmm.17584. Epub 2022 Dec 7. PMID- 36086954 OWN - NLM STAT- MEDLINE DCOM- 20230104 LR - 20230111 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 114 IP - 1 DP - 2023 Jan TI - Targeting the PTP1B-Bcr-Abl1 interaction for the degradation of T315I mutant Bcr-Abl1 in chronic myeloid leukemia. PG - 247-258 LID - 10.1111/cas.15580 [doi] AB - Small-molecule-induced degradation of mutant Bcr-Abl1 provides a potential approach to overcome Bcr-Abl1 tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML). Our previous study reported that a synthetic steroidal glycoside SBF-1 showed remarkable anti-CML activity by inducing the degradation of native Bcr-Abl1 protein. Here, we observed the comparable growth inhibition for SBF-1 in CML cells harboring T315I mutant Bcr-Abl1 in vitro and in vivo. SBF-1 triggered its degradation through disrupting the interaction between protein-tyrosine phosphatase 1B (PTP1B) and Bcr-Abl1. Using SBF-1 as a tool, we found that Tyr46 in the PTP1B catalytic domain and Tyr852 in the Bcr-Abl1 pleckstrin-homology (PH) domain are critical for their interaction. Moreover, the phosphorylation of Tyr1086 within the Bcr-Abl1 SH2 domain recruited the E3 ubiquitin ligase c-Cbl to catalyze K27-linked ubiquitin chains, which serve as a recognition signal for p62-dependent autophagic degradation. PTP1B dephosphorylated Bcr-Abl1 at Tyr1086 and prevented the recruitment of c-Cbl, leading to the stability of Bcr-Abl1. This study unravels the action mechanism of PTP1B in stabilizing Bcr-Abl1 protein and indicates that the PTP1B-Bcr-Abl1 interaction might be one of druggable targets for TKI-resistant CML with point mutations. CI - © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Elgehama, Ahmed AU - Elgehama A AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Wang, Yixuan AU - Wang Y AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Yu, Ying AU - Yu Y AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Zhou, Lin AU - Zhou L AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Chen, Zhixiu AU - Chen Z AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Wang, Liwei AU - Wang L AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Sun, Lijun AU - Sun L AD - Department of Chemistry, University of Science and Technology of China, Hefei, China. FAU - Gao, Jian AU - Gao J AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Yu, Biao AU - Yu B AD - State Key Laborary of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Academy, Shanghai, China. FAU - Shen, Yan AU - Shen Y AUID- ORCID: 0000-0002-3204-7095 AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. FAU - Xu, Qiang AU - Xu Q AD - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. LA - eng GR - 21937005/National Natural Science Foundation of China/ GR - 81974504/National Natural Science Foundation of China/ GR - BK20191251/Natural Science Foundation of Jiangsu Province/ GR - BK20210184/Natural Science Foundation of Jiangsu Province/ PT - Journal Article DEP - 20220926 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM MH - Humans MH - *Protein Kinase Inhibitors/pharmacology MH - Drug Resistance, Neoplasm/genetics MH - Fusion Proteins, bcr-abl/genetics/metabolism MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics/metabolism MH - Point Mutation PMC - PMC9807508 OTO - NOTNLM OT - Bcr-Abl1 OT - PTP1B OT - SBF-1 OT - T315I mutant OT - chronic myeloid leukemia EDAT- 2022/09/11 06:00 MHDA- 2023/01/05 06:00 CRDT- 2022/09/10 06:02 PHST- 2022/08/28 00:00 [revised] PHST- 2022/07/01 00:00 [received] PHST- 2022/09/06 00:00 [accepted] PHST- 2022/09/11 06:00 [pubmed] PHST- 2023/01/05 06:00 [medline] PHST- 2022/09/10 06:02 [entrez] AID - CAS15580 [pii] AID - 10.1111/cas.15580 [doi] PST - ppublish SO - Cancer Sci. 2023 Jan;114(1):247-258. doi: 10.1111/cas.15580. Epub 2022 Sep 26. PMID- 36266779 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230124 IS - 1365-2141 (Electronic) IS - 0007-1048 (Linking) VI - 200 IP - 3 DP - 2023 Feb TI - Trend of circulating CD34(+) cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment. PG - 315-322 LID - 10.1111/bjh.18526 [doi] AB - We evaluated CD34(+) cells in a single-centre series of 49 consecutive patients with myelofibrosis (MF) at baseline and during ruxolitinib therapy and examined any association with spleen response. The median (range) absolute number of circulating CD34(+) cells was 0.0835 (0.001-1.528) × 10(9) /L at diagnosis, and 0.123 (0.002-1.528) × 10(9) /L at ruxolitinib start. With the exception of a transient increase after 3 months of ruxolitinib therapy, a progressive reduction in CD34(+) cells count was documented, down to a minimum of 0.063 × 10(9) /L after 36 months. We then assessed the association between spleen diameter expressed as the distance from the left costal margin (outcome) and log(CD34(+) ) cells count using random-intercept and random slope multivariable regression models to take into account within subject correlation: after adjusting for time and ruxolitinib dosage, we estimated a 0.7 cm increase (95% confidence interval 0.2-1.2, p = 0.003) in spleen length for each unit increase in log(CD34(+) ) cells count (× 10(9) /L). Although our study has some limitations, mainly related to its retrospective design, our approach may introduce a reproducible and simple tool that could facilitate the assessment of spleen response more objectively in patients with MF treated with ruxolitinib. CI - © 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. FAU - Iurlo, Alessandra AU - Iurlo A AUID- ORCID: 0000-0002-4401-0812 AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Galli, Nicole AU - Galli N AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Bucelli, Cristina AU - Bucelli C AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Artuso, Silvia AU - Artuso S AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Consonni, Dario AU - Consonni D AD - Epidemiology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Cattaneo, Daniele AU - Cattaneo D AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. LA - eng GR - Italian Ministry of Health - Current research IRCCS/ PT - Journal Article DEP - 20221020 PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Nitriles) RN - 82S8X8XX8H (ruxolitinib) RN - 0 (Antigens, CD34) SB - IM MH - Humans MH - Nitriles MH - *Primary Myelofibrosis/diagnosis MH - Retrospective Studies MH - *Spleen MH - Treatment Outcome MH - Antigens, CD34 OTO - NOTNLM OT - CD34+ OT - myelofibrosis OT - response OT - ruxolitinib OT - splenomegaly EDAT- 2022/10/22 06:00 MHDA- 2023/01/21 06:00 CRDT- 2022/10/21 00:53 PHST- 2022/09/28 00:00 [revised] PHST- 2022/08/26 00:00 [received] PHST- 2022/10/08 00:00 [accepted] PHST- 2022/10/22 06:00 [pubmed] PHST- 2023/01/21 06:00 [medline] PHST- 2022/10/21 00:53 [entrez] AID - 10.1111/bjh.18526 [doi] PST - ppublish SO - Br J Haematol. 2023 Feb;200(3):315-322. doi: 10.1111/bjh.18526. Epub 2022 Oct 20. PMID- 36503148 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230124 IS - 1943-7811 (Electronic) IS - 1525-1578 (Linking) VI - 25 IP - 2 DP - 2023 Feb TI - Rapid and Automated Semiconductor-Based Next-Generation Sequencing for Simultaneous Detection of Somatic DNA and RNA Aberrations in Myeloid Neoplasms. PG - 87-93 LID - S1525-1578(22)00342-7 [pii] LID - 10.1016/j.jmoldx.2022.11.005 [doi] AB - Evaluation of suspected myeloid neoplasms involves testing for recurrent, diagnostically and therapeutically relevant genetic alterations. Current molecular testing requires multiple technologies, different domains of expertise, and unconnected workflows, resulting in variable, lengthy turnaround times that can delay treatment. To address this unmet clinical need, we evaluated the Oncomine Myeloid Assay GX panel on the Ion Torrent Genexus platform, a rapid, integrated nucleic acid to report next-generation sequencing platform for detecting clinically relevant genetic aberrations in myeloid disorders. Specimens included synthetic DNA (101 targets) and RNA (9 targets) controls and real-world nucleic acid material derived from bone marrow or peripheral blood samples (40 patients). Ion Torrent Genexus results and performance indices were compared with those obtained from clinically validated genomic testing workflows in 2 separate clinical laboratories. The Ion Torrent Genexus identified 100% of DNA and RNA control variants. For primary patient specimens, the Ion Torrent Genexus reported 82 of 107 DNA variants and 19 of 19 RNA gene fusions identified on clinically validated assays, yielding an 80% overall detection rate. Reanalysis of exported, unfiltered Ion Torrent Genexus data revealed 15 DNA variants not called by the filtered on-board bioinformatics pipeline, yielding a 92% potential detection rate. These results hold promise for the implementation of an integrated next-generation sequencing system to rapidly detect genetic aberrations, facilitating accurate, genomics-based diagnoses and accelerated time to precision therapies in myeloid neoplasms. CI - Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - Sande, Christopher M AU - Sande CM AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Wu, Rui AU - Wu R AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Yang, Guang AU - Yang G AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Sussman, Robyn T AU - Sussman RT AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Bigdeli, Ashkan AU - Bigdeli A AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Rushton, Chase AU - Rushton C AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Chitturi, Akshay AU - Chitturi A AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Patel, Jay AU - Patel J AD - ARUP Laboratories, Salt Lake City, Utah. FAU - Szankasi, Philippe AU - Szankasi P AD - ARUP Laboratories, Salt Lake City, Utah. FAU - Morrissette, Jennifer J D AU - Morrissette JJD AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Lim, Megan S AU - Lim MS AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Elenitoba-Johnson, Kojo S J AU - Elenitoba-Johnson KSJ AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: elenitk@mskcc.org. LA - eng PT - Journal Article DEP - 20221208 PL - United States TA - J Mol Diagn JT - The Journal of molecular diagnostics : JMD JID - 100893612 RN - 63231-63-0 (RNA) RN - 9007-49-2 (DNA) SB - IM MH - Humans MH - RNA/genetics MH - Mutation MH - *Myeloproliferative Disorders/diagnosis/genetics MH - *Neoplasms/genetics MH - High-Throughput Nucleotide Sequencing/methods MH - DNA/genetics MH - Semiconductors EDAT- 2022/12/13 06:00 MHDA- 2023/01/25 06:00 CRDT- 2022/12/12 09:01 PHST- 2022/06/01 00:00 [received] PHST- 2022/10/17 00:00 [revised] PHST- 2022/11/18 00:00 [accepted] PHST- 2022/12/13 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2022/12/12 09:01 [entrez] AID - S1525-1578(22)00342-7 [pii] AID - 10.1016/j.jmoldx.2022.11.005 [doi] PST - ppublish SO - J Mol Diagn. 2023 Feb;25(2):87-93. doi: 10.1016/j.jmoldx.2022.11.005. Epub 2022 Dec 8. PMID- 36202248 OWN - NLM STAT- MEDLINE DCOM- 20230117 LR - 20230117 IS - 1520-6017 (Electronic) IS - 0022-3549 (Linking) VI - 112 IP - 2 DP - 2023 Feb TI - The Application of Virtual Therapeutic Drug Monitoring to Assess the Pharmacokinetics of Imatinib in a Chinese Cancer Population Group. PG - 599-609 LID - S0022-3549(22)00450-6 [pii] LID - 10.1016/j.xphs.2022.09.028 [doi] AB - PURPOSE: Imatinib is used in gastrointestinal stromal tumours (GIST) and chronic myeloid leukaemia (CML). Oncology patients demonstrate altered physiology compared to healthy adults, e.g. reduced haematocrit, increased α-1 acid glycoprotein, decreased albumin and reduced glomerular filtration rate (GFR), which may influence imatinib pharmacokinetics. Given that Chinese cancer patients often report raised imatinib plasma concentrations and wider inter-individual variability reported in trough concentration when compared to Caucasian cancer patients, therapeutic drug monitoring (TDM) has been advocated. METHOD: This study utilised a previously validated a Chinese cancer population and assessed the impact of imatinib virtual-TDM in Chinese and Caucasian cancer populations across a dosing range from 200-800 mg daily. RESULTS: Staged dose titration to 800 mg daily, resulted in recapitulation to within the target therapeutic range for 50 % (Chinese) and 42.1% (Caucasian) subjects possessing plasma concentration < 550 ng/mL when dosed at 400 mg daily. For subjects with plasma concentrations >1500 ng/mL when dosed at 400 mg daily, a dose reduction to 200 mg once daily was able to recover 67 % (Chinese) and 87.4 % (Caucasian) patients to the target therapeutic range. CONCLUSION: Virtual TDM highlights the benefit of pharmacokinetic modelling to optimising treatments in challenging oncology population groups. CI - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Yu, He AU - Yu H AD - Aston Pharmacy School, College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, United Kingdom. FAU - Badhan, Raj K Singh AU - Badhan RKS AD - Aston Pharmacy School, College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, United Kingdom. Electronic address: r.k.s.badhan@aston.ac.uk. LA - eng PT - Journal Article DEP - 20221004 PL - United States TA - J Pharm Sci JT - Journal of pharmaceutical sciences JID - 2985195R RN - 8A1O1M485B (Imatinib Mesylate) RN - 0 (Antineoplastic Agents) RN - 0 (Pyrimidines) RN - 0 (Piperazines) RN - 0 (Benzamides) SB - IM MH - Adult MH - Humans MH - Imatinib Mesylate/therapeutic use MH - *Antineoplastic Agents MH - Drug Monitoring/methods MH - Population Groups MH - East Asian People MH - Pyrimidines MH - Piperazines MH - Benzamides MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy OTO - NOTNLM OT - Cancer OT - Chinese OT - Imatinib OT - Pharmacokinetics OT - Therapeutic drug monitoring COIS- Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/10/07 06:00 MHDA- 2023/01/18 06:00 CRDT- 2022/10/06 19:24 PHST- 2022/05/16 00:00 [received] PHST- 2022/09/28 00:00 [revised] PHST- 2022/09/28 00:00 [accepted] PHST- 2022/10/07 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] PHST- 2022/10/06 19:24 [entrez] AID - S0022-3549(22)00450-6 [pii] AID - 10.1016/j.xphs.2022.09.028 [doi] PST - ppublish SO - J Pharm Sci. 2023 Feb;112(2):599-609. doi: 10.1016/j.xphs.2022.09.028. Epub 2022 Oct 4. PMID- 36634298 OWN - NLM STAT- MEDLINE DCOM- 20230116 LR - 20230116 IS - 2473-4284 (Electronic) IS - 2473-4284 (Linking) VI - 7 DP - 2023 Jan TI - Long-Term Hematologic Improvement in a Patient With Cytopenic Myelofibrosis Treated With Pacritinib. PG - e2200523 LID - 10.1200/PO.22.00523 [doi] FAU - Yacoub, Abdulraheem AU - Yacoub A AUID- ORCID: 0000-0001-5293-4620 AD - The University of Kansas Cancer Center, Westwood, KS. FAU - Mesa, Ruben A AU - Mesa RA AUID- ORCID: 0000-0001-5880-7972 AD - UT Health San Antonio Cancer Center, San Antonio, TX. FAU - Oh, Stephen T AU - Oh ST AUID- ORCID: 0000-0002-8564-5400 AD - Washington University School of Medicine, St Louis, MO. LA - eng PT - Journal Article PL - United States TA - JCO Precis Oncol JT - JCO precision oncology JID - 101705370 RN - 0 (11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene) RN - 0 (Bridged-Ring Compounds) RN - 0 (Pyrimidines) SB - IM MH - Humans MH - *Primary Myelofibrosis/complications/drug therapy MH - *Thrombocytopenia MH - Bridged-Ring Compounds MH - Pyrimidines/therapeutic use EDAT- 2023/01/13 06:00 MHDA- 2023/01/17 06:00 CRDT- 2023/01/12 16:03 PHST- 2023/01/12 16:03 [entrez] PHST- 2023/01/13 06:00 [pubmed] PHST- 2023/01/17 06:00 [medline] AID - 10.1200/PO.22.00523 [doi] PST - ppublish SO - JCO Precis Oncol. 2023 Jan;7:e2200523. doi: 10.1200/PO.22.00523.