PMID- 32702842 OWN - NLM STAT- MEDLINE DCOM- 20200803 LR - 20200806 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 99 IP - 29 DP - 2020 Jul 17 TI - Treatment outcomes in children with Acute lymphoblastic leukemia with versus without coexisting Down's syndrome: A systematic review and meta-analysis. PG - e21015 LID - 10.1097/MD.0000000000021015 [doi] LID - e21015 AB - BACKGROUND: Down syndrome (DS) also known as Trisomy 21, is a chromosomal disorder affecting approximately 1 in 732newborns annually in the United States. Children with DS are more likely to develop acute lymphoblastic leukemia (ALL). For the management of pediatric ALL, different treatment protocols have been set up since years. However, ALL children with coexisting DS have shown to have increased therapy-related toxicities compared to those without DS. Therefore, in this study, we aimed to systematically analyze the treatment outcomes in acute ALL children with versus without coexisting DS. METHODS: Electronic databases including the Web of Science, EMBASE, Cochrane Central, MEDLINE, http://www.ClinicalTrials.gov, and Google scholar were searched for publications reporting treatment related outcomes in ALL children with versus without co-existing DS. Several treatment protocols were used accordingly. This study had a long-term follow-up time period ranging from 5 to 10 years. The RevMan 5.3 software was used to carry out this analysis. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results post analysis. RESULTS: A total number of 31,476 children with ALL enrolled between the years 1981 and 2011 were included. Among the total number of children with ALL, 1303 had coexisting DS. Our results showed that event-free survival was similar in ALL children with versus without DS (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 0.51-3.50; P = .55). Overall mortality (OR: 1.63, 95% CI: 0.86-3.10; P = .13) and participants who achieved clinical remission (OR: 1.04, 95% CI: 0.12-9.29; P = .97) were also similarly manifested. However, treatment-related mortality (OR: 4.29, 95% CI: 2.90-6.36; P = .00001) and induction failure (OR: 2.77, 95% CI: 1.08-7.07; P = .03) were significantly higher in the DS group. Also, total (OR: 1.38, 95% CI: 1.02-1.88; P = .04) and bone marrow relapses (OR: 1.29, 95% CI: 1.00-1.67; P = .05) were significantly higher in ALL children with DS. Nevertheless, central nervous system relapse (OR: 1.15, 95% CI: 0.60-2.20; P = .67), testicular relapse (OR: 0.84, 95% CI: 0.38-1.85; P = .87), and other relapses (OR: 1.12, 95% CI: 0.27-4.62; P = .88) were not significantly different when these outcomes were separately analyzed. CONCLUSION: Based on this analysis of the treatment outcomes in ALL children with versus without DS, event-free survival, overall mortality, and patients who achieved clinical remission were similar during this long-term follow-up time period. However, due to the significantly higher treatment-related mortality, induction failure, and certain relapses in ALL children with DS, new guidelines might have to focus on reconsidering or modifying treatment regimens for ALL children with DS. FAU - Liao, Wenjun AU - Liao W AD - aDepartment of Neonatology bDepartment of Oncology, Jingmen No.1 People's Hospital, Jingmen, Hubei, P.R. China. FAU - Liu, Ying AU - Liu Y LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review TA - Medicine (Baltimore) JT - Medicine JID - 2985248R SB - AIM SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects MH - Down Syndrome/*complications MH - Humans MH - Neoplasm Recurrence, Local MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*complications/*drug therapy/mortality MH - Remission Induction MH - Treatment Failure PMC - PMC7373598 COIS- The authors report no conflicts of interest. EDAT- 2020/07/25 06:00 MHDA- 2020/08/04 06:00 CRDT- 2020/07/25 06:00 PHST- 2020/07/25 06:00 [entrez] PHST- 2020/07/25 06:00 [pubmed] PHST- 2020/08/04 06:00 [medline] AID - 00005792-202007170-00037 [pii] AID - MD-D-20-01130 [pii] AID - 10.1097/MD.0000000000021015 [doi] PST - ppublish SO - Medicine (Baltimore). 2020 Jul 17;99(29):e21015. doi: 10.1097/MD.0000000000021015. PMID- 32469169 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20200727 IS - 1976-2437 (Electronic) IS - 0513-5796 (Print) IS - 0513-5796 (Linking) VI - 61 IP - 6 DP - 2020 Jun TI - Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia. PG - 452-459 LID - 10.3349/ymj.2020.61.6.452 [doi] AB - PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. MATERIALS AND METHODS: Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m²/day of fludarabine for 5 or 6 days were analyzed. RESULTS: The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26-1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II-IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. CONCLUSION: RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation. CI - © Copyright: Yonsei University College of Medicine 2020. FAU - Lee, Seung Shin AU - Lee SS AUID- ORCID: 0000-0002-8174-6861 AD - Department of Hematology and Oncology, Wonkwang University Hospital, Iksan, Korea. FAU - Jung, Sung Hoon AU - Jung SH AUID- ORCID: 0000-0003-3370-3987 AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea. FAU - Do, Young Rok AU - Do YR AUID- ORCID: 0000-0003-1631-1359 AD - Department of Hematology-Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea. FAU - Kim, Dae Sik AU - Kim DS AUID- ORCID: 0000-0001-8424-8561 AD - Division of Hematology-Oncology, Department of Internal Medicine, Guro Hospital, Korea University School of Medicine, Seoul, Korea. FAU - Lee, Ji Hyun AU - Lee JH AUID- ORCID: 0000-0003-2341-4911 AD - Department of Hematology-Oncology, Dong-A Medical Center, Dong-A University College of Medicine, Busan, Korea. FAU - Park, Han Seung AU - Park HS AUID- ORCID: 0000-0003-3577-0665 AD - Department of Hematology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea. FAU - Moon, Joon Ho AU - Moon JH AUID- ORCID: 0000-0003-3756-796X AD - Department of Hematology and Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea. FAU - Yi, Jun Ho AU - Yi JH AUID- ORCID: 0000-0003-1499-7131 AD - Division of Hematology-Oncology, Department of Medicine, Chung-Ang University, Seoul, Korea. FAU - Park, Yong AU - Park Y AUID- ORCID: 0000-0001-7909-6639 AD - Division of Hematology-Oncology, Department of Internal Medicine, Anam Hospital, Korea University School of Medicine, Seoul, Korea. FAU - Koh, Youngil AU - Koh Y AUID- ORCID: 0000-0002-5100-9473 AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea. FAU - Yhim, Ho Young AU - Yhim HY AUID- ORCID: 0000-0002-1252-5336 AD - Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea. FAU - Choi, Yunsuk AU - Choi Y AUID- ORCID: 0000-0002-7983-8089 AD - Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea. FAU - Mun, Yeung Chul AU - Mun YC AUID- ORCID: 0000-0002-1882-3983 AD - Department of Hematology and Oncology, School of Medicine, Ewha Womans University, Seoul, Korea. FAU - Lee, Won Sik AU - Lee WS AUID- ORCID: 0000-0002-7956-468X AD - Department of Hematology and Oncology, Inje University Busan Paik Hospital, Busan, Korea. FAU - Lee, Seok AU - Lee S AUID- ORCID: 0000-0002-9442-9814 AD - Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Yang, Deok Hwan AU - Yang DH AUID- ORCID: 0000-0003-2830-9889 AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea. drydh1685@hotmail.com. CN - Korean Adult Acute Lymphoblastic Leukemia Working Party LA - eng PT - Journal Article TA - Yonsei Med J JT - Yonsei medical journal JID - 0414003 RN - FA2DM6879K (Vidarabine) RN - G1LN9045DK (Busulfan) RN - P2K93U8740 (fludarabine) SB - IM MH - Acute Disease MH - Adolescent MH - Adult MH - Aged MH - Busulfan/*therapeutic use MH - Female MH - Graft vs Host Disease/etiology MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - Humans MH - Kaplan-Meier Estimate MH - Middle Aged MH - Multivariate Analysis MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*therapy MH - Proportional Hazards Models MH - Recurrence MH - *Transplantation Conditioning MH - Transplantation, Homologous MH - Vidarabine/*analogs & derivatives/therapeutic use MH - Young Adult PMC - PMC7256005 OTO - NOTNLM OT - Fludarabine OT - busulfan OT - lymphoblastic leukemia OT - stem cell transplantation OT - transplantation conditioning COIS- The authors have no potential conflicts of interest to disclose. EDAT- 2020/05/30 06:00 MHDA- 2020/07/28 06:00 CRDT- 2020/05/30 06:00 PHST- 2020/01/22 00:00 [received] PHST- 2020/04/02 00:00 [revised] PHST- 2020/04/22 00:00 [accepted] PHST- 2020/05/30 06:00 [entrez] PHST- 2020/05/30 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] AID - 61.452 [pii] AID - 10.3349/ymj.2020.61.6.452 [doi] PST - ppublish SO - Yonsei Med J. 2020 Jun;61(6):452-459. doi: 10.3349/ymj.2020.61.6.452. PMID- 32458063 OWN - NLM STAT- MEDLINE DCOM- 20200723 LR - 20200723 IS - 1432-0584 (Electronic) IS - 0939-5555 (Linking) VI - 99 IP - 7 DP - 2020 Jul TI - Comparison of central nervous system relapse outcomes following haploidentical vs identical-sibling transplant for acute lymphoblastic leukemia. PG - 1643-1653 LID - 10.1007/s00277-020-04080-9 [doi] AB - To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT. FAU - Chen, Qi AU - Chen Q AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Zhao, Xin AU - Zhao X AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Fu, Hai-Xia AU - Fu HX AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Chen, Yu-Hong AU - Chen YH AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Zhang, Yuan-Yuan AU - Zhang YY AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Wang, Jing-Zhi AU - Wang JZ AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Wang, Yu AU - Wang Y AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Yan, Chen-Hua AU - Yan CH AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Wang, Feng-Rong AU - Wang FR AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Mo, Xiao-Dong AU - Mo XD AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Han, Wei AU - Han W AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Chen, Huan AU - Chen H AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Chang, Ying-Jun AU - Chang YJ AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Xu, Lan-Ping AU - Xu LP AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Liu, Kai-Yan AU - Liu KY AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Huang, Xiao-Jun AU - Huang XJ AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. AD - Peking University Institute of Hematology, Beijing, China. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. FAU - Zhang, Xiao-Hui AU - Zhang XH AUID- ORCID: 0000-0003-0245-6792 AD - Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, China. zhangxh100@sina.com. AD - Peking University Institute of Hematology, Beijing, China. zhangxh100@sina.com. AD - National Clinical Research Center for Hematologic Disease, Beijing, China. zhangxh100@sina.com. AD - Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. zhangxh100@sina.com. LA - eng GR - 81621001/Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ GR - No. 81670116/National Natural Science Foundation of China/ GR - H2018206423/Beijing Natural Science Foundation/ GR - No. 81730004/Key Program of the National Natural Science Foundation of China/ GR - No. 7171013/Beijing Natural Science Foundation/ GR - No. Z171100001017084/Beijing Municipal Science and Technology Commission/ GR - No. 2017YFA0105500, No. 2017YFA0105503/National Key Research and Development Program of China/ PT - Comparative Study PT - Journal Article DEP - 20200526 PL - Germany TA - Ann Hematol JT - Annals of hematology JID - 9107334 SB - IM MH - Adolescent MH - Adult MH - Case-Control Studies MH - Central Nervous System Neoplasms/*epidemiology/*secondary MH - Child MH - Child, Preschool MH - Diseases in Twins/epidemiology/therapy MH - Female MH - Hematopoietic Stem Cell Transplantation/adverse effects/*methods/statistics & numerical data MH - Histocompatibility Testing/methods MH - Humans MH - Incidence MH - Male MH - Middle Aged MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology/*pathology/*therapy MH - Recurrence MH - Retrospective Studies MH - *Siblings MH - Tissue Donors/statistics & numerical data MH - *Transplantation, Haploidentical/adverse effects/statistics & numerical data MH - Transplantation, Homologous/adverse effects/statistics & numerical data MH - Treatment Outcome MH - Twins, Monozygotic/statistics & numerical data MH - Young Adult OTO - NOTNLM OT - Acute lymphoblastic leukemia OT - Central nervous system OT - Haploidentical hematopoietic stem cell transplantation OT - Prognosis OT - Relapse EDAT- 2020/05/28 06:00 MHDA- 2020/07/24 06:00 CRDT- 2020/05/28 06:00 PHST- 2020/01/08 00:00 [received] PHST- 2020/05/04 00:00 [accepted] PHST- 2020/05/28 06:00 [pubmed] PHST- 2020/07/24 06:00 [medline] PHST- 2020/05/28 06:00 [entrez] AID - 10.1007/s00277-020-04080-9 [pii] AID - 10.1007/s00277-020-04080-9 [doi] PST - ppublish SO - Ann Hematol. 2020 Jul;99(7):1643-1653. doi: 10.1007/s00277-020-04080-9. Epub 2020 May 26. PMID- 32170867 OWN - NLM STAT- MEDLINE DCOM- 20200817 LR - 20200817 IS - 1096-8652 (Electronic) IS - 0361-8609 (Linking) VI - 95 IP - 7 DP - 2020 Jul TI - Phase 2 study of hyper-CMAD with liposomal vincristine for patients with newly diagnosed acute lymphoblastic leukemia. PG - 734-739 LID - 10.1002/ajh.25784 [doi] AB - Liposomal vincristine is designed to reduce neurotoxicity and increase dose intensity delivery, and has been approved as salvage therapy in relapsed/refractory acute lymphoblastic leukemia (ALL). Our aim was to evaluate the response rate, toxicities, and outcome of adults with newly diagnosed ALL who received liposomal vincristine, rather than regular vincristine in combination with intensive chemotherapy (Hyper-CMAD). In a single-center, phase 2 study, patients ≥18 years with newly-diagnosed B-cell ALL were eligible to receive hyper-CMAD alternating with high-dose methotrexate and cytarabine. Rituximab was administered in CD20 positive ALL. Tyrosine kinase inhibitors (imatinib or dasatinib) were added in Philadelphia chromosome-positive (Ph-positive) ALL. Thirty-one patients were enrolled, median follow-up of 59 months (0.3-70). Thirteen patients (42%) had CD20 positive ALL, and 21 (68%) had Ph-positive ALL. Thirty (97%) achieved complete remission (CR). All 26 patients with abnormal karyotype achieved complete cytogenetic response (CCyR), and 27/30 (90%) achieved negative minimal residual disease status by multicolor flow cytometry. Of 20 evaluable Ph-positive ALL patients, major molecular response (MMR) was achieved in 19 patients (95%); complete molecular response (CMR) in 14 (70%). Grade 3/4 peripheral neuropathy was observed in five (16%) with all grade peripheral neuropathy in 21 (68%). With a median follow-up of 59 months, 21 (68%) patients are alive. The 5-year CR duration and survival rates were 73% and 61%, respectively. Ten (32%) patients died: one, sepsis on C1D10; four, unknown; one, post-transplant complications; four, relapse. Hyper-CMAD with liposomal vincristine is safe and demonstrated high response and survival rates in newly diagnosed ALL. CI - © 2020 Wiley Periodicals, Inc. FAU - Sasaki, Koji AU - Sasaki K AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Kantarjian, Hagop AU - Kantarjian H AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Wierda, William AU - Wierda W AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Ravandi-Kashani, Farhad AU - Ravandi-Kashani F AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Jorgensen, Jeffrey AU - Jorgensen J AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Wang, Sa A AU - Wang SA AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Khoury, Joseph AU - Khoury J AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Daver, Naval AU - Daver N AUID- ORCID: 0000-0001-7103-373X AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Burger, Jan AU - Burger J AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Di Nardo, Courtney D AU - Di Nardo CD AUID- ORCID: 0000-0001-9003-0390 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Jain, Nitin AU - Jain N AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Short, Nicholas J AU - Short NJ AUID- ORCID: 0000-0002-2983-2738 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Estrov Md, Zeev AU - Estrov Md Z AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Konopleva Md PhD, Marina AU - Konopleva Md PhD M AUID- ORCID: 0000-0002-9347-2212 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Ohanian DO, Maro AU - Ohanian DO M AUID- ORCID: 0000-0002-1689-4470 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Garcia-Manero, Guillermo AU - Garcia-Manero G AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Kadia, Tapan AU - Kadia T AUID- ORCID: 0000-0002-9892-9832 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Alvarado-Valero, Yesid AU - Alvarado-Valero Y AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Yilmaz, Musa AU - Yilmaz M AUID- ORCID: 0000-0002-4498-4895 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Pierce, Sherry AU - Pierce S AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Garris, Rebecca AU - Garris R AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Ingram, April AU - Ingram A AUID- ORCID: 0000-0003-4959-8819 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. FAU - Cortes, Jorge AU - Cortes J AD - Georgia Cancer Center, Augusta, Georgia, USA. FAU - OʼBrien, Susan AU - OʼBrien S AD - Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California, USA. FAU - Jabbour, Elias AU - Jabbour E AUID- ORCID: 0000-0003-4465-6119 AD - Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200424 PL - United States TA - Am J Hematol JT - American journal of hematology JID - 7610369 RN - 0 (Liposomes) RN - 04079A1RDZ (Cytarabine) RN - 4F4X42SYQ6 (Rituximab) RN - 5J49Q6B70F (Vincristine) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Cytarabine/administration & dosage MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Liposomes MH - Male MH - Methotrexate/administration & dosage MH - Middle Aged MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/*mortality MH - Rituximab/administration & dosage MH - Survival Rate MH - Vincristine/*administration & dosage EDAT- 2020/03/15 06:00 MHDA- 2020/08/18 06:00 CRDT- 2020/03/15 06:00 PHST- 2019/12/30 00:00 [received] PHST- 2020/03/04 00:00 [revised] PHST- 2020/03/10 00:00 [accepted] PHST- 2020/03/15 06:00 [pubmed] PHST- 2020/08/18 06:00 [medline] PHST- 2020/03/15 06:00 [entrez] AID - 10.1002/ajh.25784 [doi] PST - ppublish SO - Am J Hematol. 2020 Jul;95(7):734-739. doi: 10.1002/ajh.25784. Epub 2020 Apr 24. PMID- 32052094 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20200727 IS - 1432-072X (Electronic) IS - 0302-8933 (Linking) VI - 202 IP - 5 DP - 2020 Jul TI - Microbial L-asparaginase: purification, characterization and applications. PG - 967-981 LID - 10.1007/s00203-020-01814-1 [doi] AB - L-asparaginase (E.C.3.5.1.1) is an important enzyme that has been purified and characterized for over decades to study and evaluate its anti-carcinogenic activity against different lymphoproliferative disorders such as acute lymphoblastic leukemia (ALL) and Hodgkin's lymphoma. The ability of the enzyme to convert L-asparagine into aspartic acid and ammonia is the reason behind its anti-cancerous activity. Apart from its medicinal uses, it is widely used in food industry to tackle acrylamide, a probable human carcinogen and, production in carbohydrate-rich foods cooked at high temperatures. There are variety of organisms including microorganisms such as bacteria, fungi, algae, and plants that produce L-asparaginase. The enzyme obtained from different microbial and plant sources have different physiochemical properties and kinetic parameters. L-asparaginases have an optimum pH range between 6 and 10 and an optimum temperature between 37 and 85 °C. This article has reviewed the lowest molecular mass for L-asparaginase in Yersinia pseudotuberculosis Q66CJ2 which is 36.27 kDa, while the highest for Pseudomonas otitidis which has a molecular mass of 205 ± 3 kDa. This review is an attempt to summarize most of the available sources, their phylogenetic relationships, purification methods, data regarding different physiochemical and kinetic properties of L-asparaginase. FAU - Muneer, Faizan AU - Muneer F AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. FAU - Siddique, Muhammad Hussnain AU - Siddique MH AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. FAU - Azeem, Farrukh AU - Azeem F AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. FAU - Rasul, Ijaz AU - Rasul I AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. FAU - Muzammil, Saima AU - Muzammil S AD - Department of Microbiology, Government College University, Faisalabad, Pakistan. FAU - Zubair, Muhammad AU - Zubair M AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. FAU - Afzal, Muhammad AU - Afzal M AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. FAU - Nadeem, Habibullah AU - Nadeem H AUID- ORCID: 0000-0003-4290-5492 AD - Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan. habibullah@gcuf.edu.pk. LA - eng PT - Journal Article PT - Review DEP - 20200212 PL - Germany TA - Arch Microbiol JT - Archives of microbiology JID - 0410427 RN - 30KYC7MIAI (Aspartic Acid) RN - 7006-34-0 (Asparagine) RN - 7664-41-7 (Ammonia) RN - EC 3.5.1.1 (Asparaginase) SB - IM MH - Ammonia/metabolism MH - Asparaginase/*chemistry/genetics/isolation & purification MH - Asparagine/chemistry MH - Aspartic Acid/metabolism MH - Bacteria/*enzymology MH - Fungi/*enzymology MH - Hodgkin Disease/*drug therapy MH - Humans MH - Phylogeny MH - Plants MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy OTO - NOTNLM OT - Acrylamide OT - Asparagine OT - Biosensor OT - Biosynthesis OT - Chromatography OT - Hodgkin’s lymphoma OT - Lymphoblastic leukemia OT - Millard reaction OT - Phylogenetic tree EDAT- 2020/02/14 06:00 MHDA- 2020/07/28 06:00 CRDT- 2020/02/14 06:00 PHST- 2019/11/06 00:00 [received] PHST- 2020/01/21 00:00 [accepted] PHST- 2020/01/02 00:00 [revised] PHST- 2020/02/14 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2020/02/14 06:00 [entrez] AID - 10.1007/s00203-020-01814-1 [pii] AID - 10.1007/s00203-020-01814-1 [doi] PST - ppublish SO - Arch Microbiol. 2020 Jul;202(5):967-981. doi: 10.1007/s00203-020-01814-1. Epub 2020 Feb 12. PMID- 31796666 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20200727 IS - 1875-8592 (Electronic) IS - 1574-0153 (Linking) VI - 27 IP - 2 DP - 2020 TI - Significance of NOTCH1 mutations détections in T-acute lymphoblastic leukemia patients. PG - 157-162 LID - 10.3233/CBM-190967 [doi] AB - BACKGROUND: This study aimed to determine the prevalence and clinical impact of neurogenic locus notch homolog protein 1 (NOTCH1) mutations among patients with T cell acute lymphoblastic leukemia (T-ALL). PATIENT AND METHODS: A cohort of 60 T-ALL cases was included in this study. Sanger sequencing were done for NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline, glutamic acid, serine, threonine (PEST) domains in all studied T ALL patients at diagnosis. RESULTS: NOTCH1 mutations was detected in 40 out of 60 T-ALL patients (66%). Mutations in T-ALL patients are deletions (22 mutations) and point mutation (10 mutations). NOTCH1 mutations was found to have no significant impact on clinical outcome and prognosis in T-ALL including overall survival, progression free survival, relapse and mortality (P> 0.05 for all). CONCLUSION: NOTCH1 mutations were frequently detected in T All patients; however, these mutations did not affect the T ALL patient's outcome. The high prevalence of NOTCH1 mutations at diagnosis could be used for detection of minimal residual disease in T ALL. FAU - Aref, Salah AU - Aref S FAU - El Agdar, Mohammed AU - El Agdar M FAU - Salama, Osama AU - Salama O FAU - Zeid, Tarek Abouzeid AU - Zeid TA FAU - Sabry, Mohamed AU - Sabry M LA - eng PT - Journal Article PL - Netherlands TA - Cancer Biomark JT - Cancer biomarkers : section A of Disease markers JID - 101256509 RN - 0 (NOTCH1 protein, human) RN - 0 (Receptor, Notch1) SB - IM MH - Adult MH - Cohort Studies MH - Female MH - Humans MH - Male MH - *Mutation MH - Neoplasm, Residual/genetics/pathology MH - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/*pathology MH - Prognosis MH - Receptor, Notch1/*genetics MH - Survival Rate OTO - NOTNLM OT - NOTCH1 OT - T-ALL OT - mutations OT - prognosis EDAT- 2019/12/05 06:00 MHDA- 2020/07/28 06:00 CRDT- 2019/12/05 06:00 PHST- 2019/12/05 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2019/12/05 06:00 [entrez] AID - CBM190967 [pii] AID - 10.3233/CBM-190967 [doi] PST - ppublish SO - Cancer Biomark. 2020;27(2):157-162. doi: 10.3233/CBM-190967. PMID- 31766014 OWN - NLM STAT- MEDLINE DCOM- 20200811 LR - 20200811 IS - 1540-1413 (Electronic) IS - 1540-1405 (Linking) VI - 17 IP - 11.5 DP - 2019 Nov TI - Management of Recurrent Acute Lymphoblastic Leukemia With T-Cell Engagement: CAR T, BiTEs, and Beyond. PG - 1448-1450 LID - jnccn20195030 [pii] LID - 10.6004/jnccn.2019.5030 [doi] AB - Immunotherapies targeting CD19 (blinatumomab) and CD22 (inotuzumab ozogamicin) have demonstrated higher complete response rates and improved survival compared with chemotherapy in relapsed/refractory acute lymphoblastic leukemia (ALL), and are now standard of care in the relapsed setting. However, most adult patients still die of ALL despite these therapies, with or without hematopoietic stem cell transplant. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Jae Park summarized clinical data from key trials of novel immunotherapies in ALL and reviewed evidence-based treatment approaches for adults with relapsed/refractory B-cell ALL. FAU - Park, Jae AU - Park J LA - eng PT - Journal Article PL - United States TA - J Natl Compr Canc Netw JT - Journal of the National Comprehensive Cancer Network : JNCCN JID - 101162515 RN - 0 (Receptors, Chimeric Antigen) SB - IM MH - Humans MH - Neoplasm Recurrence, Local MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy MH - Receptors, Chimeric Antigen/*metabolism MH - T-Lymphocytes/*immunology EDAT- 2019/11/26 06:00 MHDA- 2020/08/12 06:00 CRDT- 2019/11/26 06:00 PHST- 2019/11/26 06:00 [entrez] PHST- 2019/11/26 06:00 [pubmed] PHST- 2020/08/12 06:00 [medline] AID - jnccn20195030 [pii] AID - 10.6004/jnccn.2019.5030 [doi] PST - ppublish SO - J Natl Compr Canc Netw. 2019 Nov;17(11.5):1448-1450. doi: 10.6004/jnccn.2019.5030. PMID- 31648325 OWN - NLM STAT- MEDLINE DCOM- 20200817 LR - 20200817 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 3 IP - 20 DP - 2019 Oct 22 TI - Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia. PG - 3033-3037 LID - 10.1182/bloodadvances.2019000457 [doi] AB - Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179. CI - © 2019 by The American Society of Hematology. FAU - Gökbuget, Nicola AU - Gökbuget N AD - Department of Medicine II, Goethe University, Frankfurt, Germany. FAU - Kantarjian, Hagop M AU - Kantarjian HM AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Brüggemann, Monika AU - Brüggemann M AD - University Schleswig Holstein in the City Hospital, Kiel, Germany. FAU - Stein, Anthony S AU - Stein AS AD - City of Hope, Duarte, CA. FAU - Bargou, Ralf C AU - Bargou RC AD - Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany. FAU - Dombret, Hervé AU - Dombret H AD - Hôpital Saint Louis, University of Paris, Paris, France. FAU - Fielding, Adele K AU - Fielding AK AD - UCL Cancer Institute, University College London, London, United Kingdom. FAU - Heffner, Leonard AU - Heffner L AD - Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA. FAU - Rigal-Huguet, Françoise AU - Rigal-Huguet F AD - Centre Hospitalier Universitaire de Toulouse, Toulouse, France. FAU - Litzow, Mark AU - Litzow M AD - Division of Hematology, Mayo Clinic, Rochester, MN. FAU - O'Brien, Susan AU - O'Brien S AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Zugmaier, Gerhard AU - Zugmaier G AD - Amgen Research (Munich) GmbH, Munich, Germany. FAU - Gao, Shan AU - Gao S AD - Amgen, Inc., Washington, DC. FAU - Nagorsen, Dirk AU - Nagorsen D AD - Amgen, Inc., Thousand Oaks, CA; and. FAU - Forman, Stephen J AU - Forman SJ AD - City of Hope, Duarte, CA. FAU - Topp, Max S AU - Topp MS AD - Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany. LA - eng SI - ClinicalTrials.gov/NCT01466179 PT - Journal Article PT - Research Support, Non-U.S. Gov't TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (Antibodies, Bispecific) RN - 0 (Antineoplastic Agents) RN - 4FR53SIF3A (blinatumomab) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antibodies, Bispecific/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use MH - Clinical Trials, Phase II as Topic MH - Combined Modality Therapy/methods MH - Drug Resistance, Neoplasm MH - Female MH - Hematopoietic Stem Cell Transplantation MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/mortality/pathology MH - Prognosis MH - Recurrence MH - Treatment Outcome MH - Young Adult PMC - PMC6849936 COIS- Conflict-of-interest disclosure: N.G. received research funding from Amgen, Pfizer, and Novartis; received advisory board and speaker fees from Amgen, Pfizer, and Novartis; received travel grants from Amgen, Pfizer, and Novartis; and received advisory board honoraria from Kite/Gilead and Celgene. H.M.K. received research funding from AbbVie, Agios, Amgen, Ariad, Astex, Bristol-Myers Squibb, Cyclacel, ImmunoGen, Jazz, and Pfizer and received honoraria from AbbVie, Actinium, Agios, Amgen, ImmunoGen, Orsinex, Pfizer, and Takeda. M.B. received research funding from Amgen; received reference diagnostics from Affimed, Amgen, and Regeneron; received consulting fees from PRMA Consulting, Ltd; and received speaker fees from Amgen, Hoffman-La Roche, Incyte, and Pfizer. A.S.S. received speaker fees from Amgen and Celgene. R.C.B. received fees for advisory activities from Amgen, AstraZeneca, Cellex, GEMoaB Monoclonals, GmbH, Molecular Partners, Novartis, and Pfizer; and has a blinatumomab patent with royalties paid. H.D. received research funding from Amgen, Incyte/Ariad, Novartis, Pfizer, and Servier; received consultancy fees from Amgen, Celgene, Cellectis, and Pfizer; received advisor honoraria from Amgen, Celgene, Cellectis, Incyte/Ariad, Novartis, Pfizer, Servier, and Shire/Baxalta; and received speaker fees from Amgen, Celgene, Incyte/Ariad, and Pfizer. L.H. received institutional research funding from AbbVie, ADC Therapeutics, Astex Pharmaceuticals, Genentech, and Pharmacyclics and received personal fees from Pharmacyclics. F.R.-H. received advisory board fees from Amgen, Bristol-Myers Squibb, Incyte, Jazz Pharmaceuticals, Novartis, and Pfizer. M.L. received research funding from Amgen. S.O. received consultancy fees from Amgen. G.Z. is an employee of Amgen and holds several pending patents. S.G. is a former employee of Amgen. D.N. is an employee and stockholder of Amgen and holds blinatumomab-related pending patents. M.S.T. received research funding and personal fees from Amgen. The remaining authors declare no competing financial interests. EDAT- 2019/10/28 06:00 MHDA- 2020/08/18 06:00 CRDT- 2019/10/25 06:00 PHST- 2019/05/16 00:00 [received] PHST- 2019/09/16 00:00 [accepted] PHST- 2019/10/25 06:00 [entrez] PHST- 2019/10/28 06:00 [pubmed] PHST- 2020/08/18 06:00 [medline] AID - 407210 [pii] AID - 2019/ADV2019000457 [pii] AID - 10.1182/bloodadvances.2019000457 [doi] PST - ppublish SO - Blood Adv. 2019 Oct 22;3(20):3033-3037. doi: 10.1182/bloodadvances.2019000457. PMID- 31611626 OWN - NLM STAT- MEDLINE DCOM- 20200731 LR - 20200731 IS - 1476-5551 (Electronic) IS - 0887-6924 (Linking) VI - 34 IP - 2 DP - 2020 Feb TI - T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol. PG - 347-357 LID - 10.1038/s41375-019-0598-2 [doi] AB - The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD ≥ 5% on day 29 or ≥0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults. FAU - Quist-Paulsen, P AU - Quist-Paulsen P AD - Department of Hematology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. Petter.Quist-Paulsen@ntnu.no. FAU - Toft, N AU - Toft N AD - Department of Hematology, Herlev University Hospital, University of Copenhagen, Herlev, Denmark. FAU - Heyman, M AU - Heyman M AD - Childhood Cancer Research Unit, Karolinska Institute, Astrid Lindgren's Childrens' Hospital, Karolinska University Hospital, Stockholm, Sweden. FAU - Abrahamsson, J AU - Abrahamsson J AD - Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Griškevičius, L AU - Griškevičius L AD - Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania. FAU - Hallböök, H AU - Hallböök H AD - Department of Medical Sciences, Uppsala University, Uppsala, Sweden. FAU - Jónsson, Ó G AU - Jónsson ÓG AD - Children's Hospital, Landspitali University Hospital, Reykjavík, Iceland. FAU - Palk, K AU - Palk K AD - Department of Hematology, North Estonia Medical Centre, Tallinn, Estonia. FAU - Vaitkeviciene, G AU - Vaitkeviciene G AD - Centre for Pediatric Oncology and Hematology, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius University, Vilnius, Lithuania. FAU - Vettenranta, K AU - Vettenranta K AD - Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. FAU - Åsberg, A AU - Åsberg A AD - Department of Pediatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. FAU - Frandsen, T L AU - Frandsen TL AD - Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark. FAU - Opdahl, S AU - Opdahl S AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, NTNU, Trondheim, Norway. FAU - Marquart, H V AU - Marquart HV AD - Department of Clinical Immunology, Section 7631, University Hospital Rigshospitalet, Copenhagen, Denmark. FAU - Siitonen, S AU - Siitonen S AD - Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland. FAU - Osnes, L T AU - Osnes LT AD - Department of Immunology, Oslo University Hospital, Oslo, Norway. FAU - Hultdin, M AU - Hultdin M AD - Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. FAU - Overgaard, U M AU - Overgaard UM AD - Department of Hematology, The University Hospital Rigshospitalet, Copenhagen, Denmark. FAU - Wartiovaara-Kautto, U AU - Wartiovaara-Kautto U AD - Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland. FAU - Schmiegelow, K AU - Schmiegelow K AUID- ORCID: 0000-0002-0829-4993 AD - Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark. AD - Institute Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article DEP - 20191014 PL - England TA - Leukemia JT - Leukemia JID - 8704895 SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Child MH - Child, Preschool MH - Female MH - Hematopoietic Stem Cell Transplantation MH - Humans MH - Infant MH - Male MH - Middle Aged MH - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality/*therapy MH - Treatment Outcome MH - Young Adult EDAT- 2019/10/16 06:00 MHDA- 2020/08/01 06:00 CRDT- 2019/10/16 06:00 PHST- 2019/06/06 00:00 [received] PHST- 2019/09/30 00:00 [accepted] PHST- 2019/09/16 00:00 [revised] PHST- 2019/10/16 06:00 [pubmed] PHST- 2020/08/01 06:00 [medline] PHST- 2019/10/16 06:00 [entrez] AID - 10.1038/s41375-019-0598-2 [pii] AID - 10.1038/s41375-019-0598-2 [doi] PST - ppublish SO - Leukemia. 2020 Feb;34(2):347-357. doi: 10.1038/s41375-019-0598-2. Epub 2019 Oct 14. PMID- 31566728 OWN - NLM STAT- MEDLINE DCOM- 20200805 LR - 20200805 IS - 1365-2141 (Electronic) IS - 0007-1048 (Linking) VI - 188 IP - 2 DP - 2020 Jan TI - Targeted therapy paves the way for the cure of acute lymphoblastic leukaemia. PG - 207-223 LID - 10.1111/bjh.16207 [doi] AB - The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T- cell therapy. A number of new therapies have been approved by the US Food and Drug Administration in the past 5 years, including blinatumomab in 2014, inotuzumab ozagamicin in 2017 and tisagenlecleucel in 2017 for relapsed/refractory ALL. This has led to tremendous improvement in long-term survival, of more than 50% in patients with precursor B-ALL [50-70% in patients with Philadelphia chromosome (Ph)-positive ALL)], 50-60% in T-ALL and 80% in mature B-ALL. Research is ongoing to optimize the benefit of targeted therapeutics with the goal of decreasing the use of cytotoxic therapies. CI - © 2019 British Society for Haematology and John Wiley & Sons Ltd. FAU - Rafei, Hind AU - Rafei H AUID- ORCID: 0000-0002-5724-4183 AD - Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kantarjian, Hagop M AU - Kantarjian HM AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Jabbour, Elias J AU - Jabbour EJ AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LA - eng PT - Journal Article PT - Review DEP - 20190930 PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Antineoplastic Agents, Immunological) SB - IM MH - Antineoplastic Agents, Immunological/pharmacology/*therapeutic use MH - Humans MH - Middle Aged MH - Philadelphia Chromosome MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/pathology OTO - NOTNLM OT - *acute lymphoblastic leukaemia OT - *bispecific antibodies OT - *chimeric antigen receptor-T cell therapy OT - *monoclonal antibodies OT - *tyrosine kinase inhibitors EDAT- 2019/10/01 06:00 MHDA- 2020/08/06 06:00 CRDT- 2019/10/01 06:00 PHST- 2019/10/01 06:00 [pubmed] PHST- 2020/08/06 06:00 [medline] PHST- 2019/10/01 06:00 [entrez] AID - 10.1111/bjh.16207 [doi] PST - ppublish SO - Br J Haematol. 2020 Jan;188(2):207-223. doi: 10.1111/bjh.16207. Epub 2019 Sep 30. PMID- 31464164 OWN - NLM STAT- MEDLINE DCOM- 20200723 LR - 20200723 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 28 IP - 20 DP - 2019 Oct 15 TI - A New Conditioning Regimen Can Significantly Promote Post-Transplant Immune Reconstitution and Improve the Outcome of Umbilical Cord Blood Transplantation for Patients. PG - 1376-1383 LID - 10.1089/scd.2019.0139 [doi] AB - This study included data from 81 consecutively enrolled patients with hematological diseases who had been treated with unrelated umbilical cord blood transplantation (UCBT) between September 2014 and April 2019. All patients received intense conditioning regimens with combined fludarabine and high-dose cyclophosphamide (FC) before undergoing UCBT. Sixty-seven patients received a single UCBT, and 14 patients received a double UCBT. Fifty patients were pretreated with the fludarabine, busulfan, and cyclophosphamide (FBC) protocol, while 31 patients were treated with FC before transplantation. Graft-versus-host disease (GVHD) was prevented with cyclosporine A and mycophenolate mofetil administration. According to low-resolution, human leukocyte antigen (HLA) donor-recipient matching at six sites, 53 patients had 5-6 matches, while 28 patients had 4 matches. Seventy-eight patients (96.3%) achieved complete engraftment in this study. Thirty-six patients developed acute GVHD (aGVHD). The cumulative incidence of grade I-II aGVHD at day 100 posthematopoietic stem cell transplantation was 29.6%, and the cumulative incidence of grade III-IV aGVHD was 14.8%. At the end of the follow-up, 12 patients died due to treatment-related complications, and 4 died of disease relapse after transplantation. The transplant-related deaths were due to transplant-related infection (8 of 81), GVHD (2 of 81), and organ toxicity (2 of 81). The probability of overall survival (OS) was 80.2%. A higher dose of cyclophosphamide combined with fludarabine conditioning in UCBT was an effective curative method for treatment of hematologic disorders and could enhance the engraftment of umbilical cord blood stem cells, promote post-transplant immune reconstitution, and improve OS. FAU - Yu, Zheng-Ping AU - Yu ZP AD - Department of Hematology (Key Department of Jiangsu Medicine), Zhong Da Hospital, Southeast University, Nanjing, China. FAU - Ding, Jia-Hua AU - Ding JH AD - Department of Hematology (Key Department of Jiangsu Medicine), Zhong Da Hospital, Southeast University, Nanjing, China. FAU - Sun, Ai-Ning AU - Sun AN AD - Hematology Division, Soochow University Affiliated No 1 People's Hospital, Suzhou, China. FAU - Chen, Bao-An AU - Chen BA AD - Department of Hematology (Key Department of Jiangsu Medicine), Zhong Da Hospital, Southeast University, Nanjing, China. FAU - Ge, Zheng AU - Ge Z AD - Department of Hematology (Key Department of Jiangsu Medicine), Zhong Da Hospital, Southeast University, Nanjing, China. FAU - Wu, De-Pei AU - Wu DP AD - Hematology Division, Soochow University Affiliated No 1 People's Hospital, Suzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190926 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Antilymphocyte Serum) RN - 0 (Immunosuppressive Agents) RN - 04079A1RDZ (Cytarabine) RN - 13909-09-6 (Semustine) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 8N3DW7272P (Cyclophosphamide) RN - FA2DM6879K (Vidarabine) RN - G1LN9045DK (Busulfan) RN - P2K93U8740 (fludarabine) SB - IM MH - Adult MH - Anemia, Aplastic/*drug therapy/immunology/mortality/pathology MH - Antilymphocyte Serum/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Busulfan/administration & dosage MH - *Cord Blood Stem Cell Transplantation MH - Cyclophosphamide/administration & dosage MH - Cytarabine/administration & dosage MH - Female MH - Graft Survival MH - Graft vs Host Disease/physiopathology/prevention & control MH - Granulocyte Colony-Stimulating Factor/administration & dosage MH - Humans MH - *Immune Reconstitution MH - Immunosuppressive Agents/therapeutic use MH - Leukemia, Myeloid, Acute/*drug therapy/immunology/mortality/pathology MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/*drug therapy/immunology/mortality/pathology MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/immunology/mortality/pathology MH - Primary Immunodeficiency Diseases/*drug therapy/immunology/mortality/pathology MH - Semustine/administration & dosage MH - Survival Analysis MH - Transplantation Conditioning/*methods MH - Transplantation, Homologous MH - Treatment Outcome MH - Unrelated Donors MH - Vidarabine/administration & dosage/analogs & derivatives OTO - NOTNLM OT - *Allo-hematopoietic stem cell transplantation OT - *cord blood transplantation OT - *hematologic system diseases EDAT- 2019/08/30 06:00 MHDA- 2020/07/24 06:00 CRDT- 2019/08/30 06:00 PHST- 2019/08/30 06:00 [pubmed] PHST- 2020/07/24 06:00 [medline] PHST- 2019/08/30 06:00 [entrez] AID - 10.1089/scd.2019.0139 [doi] PST - ppublish SO - Stem Cells Dev. 2019 Oct 15;28(20):1376-1383. doi: 10.1089/scd.2019.0139. Epub 2019 Sep 26. PMID- 31444252 OWN - NLM STAT- MEDLINE DCOM- 20200803 LR - 20200803 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 26 IP - 2 DP - 2020 Jan 15 TI - FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in Children and Young Adults. PG - 328-331 LID - 10.1158/1078-0432.CCR-19-1255 [doi] AB - On December 20, 2018, the Food and Drug Administration approved calaspargase pegol-mknl (CALASP), an asparagine-specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Efficacy was determined on the basis of achievement and maintenance of steady-state nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using CALASP, 2,500 U/m(2) intravenously, every 3 weeks. In a randomized comparison to pegaspargase (PEGASP) every 2 weeks, treatment with CALASP every 3 weeks had a similar safety profile and no substantial impairment in event-free survival. The pharmacokinetics of CALASP were studied when administered in combination with multiagent chemotherapy in 124 patients with B-cell ALL in Study AALL07P4 and Study DFCI 11-001. The results showed that 123 [99%, 95% confidence interval (CI), 96%-100%] of the 124 patients maintained NSAA >0.1 U/mL at weeks 6, 12, 18, 24, and 30 of post-induction phase. Maintaining adequate NSAA levels is critical to successful treatment of ALL. Herein, we describe the FDA review and approval of CALASP.See related commentary by Lew, p. 325. CI - ©2019 American Association for Cancer Research. FAU - Li, Ruo-Jing AU - Li RJ AUID- ORCID: 0000-0001-7559-3929 AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. ruojing.li@fda.hhs.gov. FAU - Jin, Runyan AU - Jin R AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Liu, Chao AU - Liu C AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Cao, Xianhua AU - Cao X AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Manning, Michael L AU - Manning ML AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Di, Xu Michael AU - Di XM AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Przepiorka, Donna AU - Przepiorka D AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Namuswe, Frances AU - Namuswe F AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Deisseroth, Albert AU - Deisseroth A AD - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Goldberg, Kirsten B AU - Goldberg KB AUID- ORCID: 0000-0001-8659-1240 AD - Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Blumenthal, Gideon M AU - Blumenthal GM AD - Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland. FAU - Pazdur, Richard AU - Pazdur R AD - Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland. LA - eng PT - Comment PT - Journal Article DEP - 20190823 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antineoplastic Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - EC 3.5.1.1 (Asparaginase) RN - EC 3.5.1.1 (calaspargase pegol) SB - IM CIN - Clin Cancer Res. 2020 Jan 15;26(2):325-327. PMID: 31641006 CON - Clin Cancer Res. 2020 Jan 15;26(2):325-327. PMID: 31641006 MH - *Antineoplastic Agents MH - Asparaginase MH - Child MH - Disease-Free Survival MH - Humans MH - Polyethylene Glycols MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma MH - Young Adult EDAT- 2019/08/25 06:00 MHDA- 2020/08/04 06:00 CRDT- 2019/08/25 06:00 PHST- 2019/04/19 00:00 [received] PHST- 2019/06/06 00:00 [revised] PHST- 2019/08/21 00:00 [accepted] PHST- 2019/08/25 06:00 [pubmed] PHST- 2020/08/04 06:00 [medline] PHST- 2019/08/25 06:00 [entrez] AID - 1078-0432.CCR-19-1255 [pii] AID - 10.1158/1078-0432.CCR-19-1255 [doi] PST - ppublish SO - Clin Cancer Res. 2020 Jan 15;26(2):328-331. doi: 10.1158/1078-0432.CCR-19-1255. Epub 2019 Aug 23. PMID- 31307896 OWN - NLM STAT- MEDLINE DCOM- 20200806 LR - 20200806 IS - 2152-2669 (Electronic) IS - 2152-2669 (Linking) VI - 19 IP - 8 DP - 2019 Aug TI - SOHO State of the Art Update and Next Questions: Advances in the Treatment of Adult Acute Lymphoblastic Leukemia. PG - 471-479 LID - S2152-2650(19)30579-8 [pii] LID - 10.1016/j.clml.2019.06.011 [doi] AB - The treatment of adult acute lymphoblastic leukemia (ALL) has largely followed the successful pediatric model that uses multi-agent chemotherapy regimens. Although cytotoxic chemotherapy can induce complete remissions, elderly patients are frequently unable to tolerate its intensity owing to toxicities and comorbidities. Elderly patients particularly often relapse, leading to a 5-year overall survival (OS) of only 20%. In an effort to improve outcomes while minimizing toxicities, novel targeted therapies have been developed: monoclonal antibodies against CD19, CD20, and CD22; tyrosine kinase inhibitors; chimeric antigen receptor T-cell therapies; and BH3 mimetics. Here, we discuss advancements in the treatment of ALL and their places in the armamentarium for adult patients. CI - Copyright © 2019 Elsevier Inc. All rights reserved. FAU - Paul, Shilpa AU - Paul S AD - Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Rausch, Caitlin R AU - Rausch CR AD - Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Welch, Mary Alma AU - Welch MA AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Kantarjian, Hagop M AU - Kantarjian HM AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Jabbour, Elias J AU - Jabbour EJ AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: ejabbour@mdanderson.org. LA - eng PT - Journal Article PT - Review DEP - 20190703 PL - United States TA - Clin Lymphoma Myeloma Leuk JT - Clinical lymphoma, myeloma & leukemia JID - 101525386 RN - 0 (Antigens, Neoplasm) RN - 0 (Antineoplastic Agents, Immunological) SB - IM MH - Adult MH - Antigens, Neoplasm/*immunology MH - Antineoplastic Agents, Immunological/*therapeutic use MH - Humans MH - Immunotherapy/*methods MH - *Molecular Targeted Therapy MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology/*therapy MH - Prognosis MH - Survival Rate OTO - NOTNLM OT - *Blinatumomab OT - *Chimeric antigen receptor T-cell therapy OT - *Inotuzumab ozogamicin OT - *Monoclonal antibodies OT - *Tyrosine kinase inhibitors EDAT- 2019/07/17 06:00 MHDA- 2020/08/07 06:00 CRDT- 2019/07/17 06:00 PHST- 2019/06/05 00:00 [received] PHST- 2019/06/26 00:00 [accepted] PHST- 2019/07/17 06:00 [pubmed] PHST- 2020/08/07 06:00 [medline] PHST- 2019/07/17 06:00 [entrez] AID - S2152-2650(19)30579-8 [pii] AID - 10.1016/j.clml.2019.06.011 [doi] PST - ppublish SO - Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):471-479. doi: 10.1016/j.clml.2019.06.011. Epub 2019 Jul 3. PMID- 31173486 OWN - NLM STAT- MEDLINE DCOM- 20200803 LR - 20200803 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 8 IP - 9 DP - 2019 Aug TI - Is hyperdiploidy a favorable cytogenetics in adults with B-lymphoblastic leukemia? PG - 4093-4099 LID - 10.1002/cam4.2255 [doi] AB - Hyperdiploidy (chromosomal number 51-65) is a common cytogenetic abnormality in pediatric patients with B-lymphoblastic leukemia (B-ALL) and belongs to the favorable cytogenetic subgroup. Hyperdiploidy in adult B-ALL is much less common and its clinical significance has not been well studied. Among the 1205 patients with B-ALL (1018 adults and 187 children) from our institution, 78 had a hyperdiploid karyotype, including 45 (4.4%) adults and 33 (17.6%) children (P < 0.0001). Among the patients with hyperdiploid B-ALL, the adult group had a significantly inferior survival (similar to the patients with a normal karyotype) compared with the pediatric group (median survival: 42 months vs undefined, P = 0.0029). Hyperdiploidy in adults B-ALL tended to more frequently harbor structural abnormalities (two or more) than children (53% vs 33%). Two or more structural abnormalities in a hyperdiploidy correlated with an adverse survival in adult patients (33 months vs undefined, P = 0.0008), similar to the survival of patients with a complex karyotype. We conclude that hyperdiploidy in adults with B-ALL is less favorable and more commonly contains structural abnormalities comparing to pediatric patients. We suggest that hyperdiploidy with two or more structural abnormalities are best considered as a complex karyotype in adults with B-ALL. CI - © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Chen, Zhining AU - Chen Z AUID- ORCID: 0000-0002-9818-8640 AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. AD - Department of Pathology, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China. FAU - Sun, Yi AU - Sun Y AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Xie, Wei AU - Xie W AUID- ORCID: 0000-0003-1815-7666 AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Wang, Sa A AU - Wang SA AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Hu, Shimin AU - Hu S AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Li, Shaoying AU - Li S AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Tang, Zhenya AU - Tang Z AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Toruner, Gokce AU - Toruner G AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Medeiros, L Jeffrey AU - Medeiros LJ AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Tang, Guilin AU - Tang G AUID- ORCID: 0000-0002-9482-4806 AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. LA - eng PT - Comparative Study PT - Journal Article DEP - 20190607 TA - Cancer Med JT - Cancer medicine JID - 101595310 SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - *Aneuploidy MH - Child MH - Child, Preschool MH - Female MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Infant MH - Karyotyping/*methods MH - Male MH - Middle Aged MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/*mortality MH - Sequence Analysis, DNA MH - Survival MH - Translocation, Genetic MH - Young Adult PMC - PMC6675728 OTO - NOTNLM OT - *B-ALL OT - *adult OT - *hyperdiploidy OT - *pediatric OT - *prognosis EDAT- 2019/06/08 06:00 MHDA- 2020/08/04 06:00 CRDT- 2019/06/08 06:00 PHST- 2018/12/20 00:00 [received] PHST- 2019/04/10 00:00 [revised] PHST- 2019/05/06 00:00 [accepted] PHST- 2019/06/08 06:00 [pubmed] PHST- 2020/08/04 06:00 [medline] PHST- 2019/06/08 06:00 [entrez] AID - CAM42255 [pii] AID - 10.1002/cam4.2255 [doi] PST - ppublish SO - Cancer Med. 2019 Aug;8(9):4093-4099. doi: 10.1002/cam4.2255. Epub 2019 Jun 7. PMID- 31081970 OWN - NLM STAT- MEDLINE DCOM- 20200817 LR - 20200817 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 120 IP - 9 DP - 2019 Sep TI - Overlapped differentially expressed genes between acute lymphoblastic leukemia and chronic lymphocytic leukemia revealed potential key genes and pathways involved in leukemia. PG - 15980-15988 LID - 10.1002/jcb.28876 [doi] AB - Common differentially expressed genes (DEGs) in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) might play critical roles in the pathogenesis and process of leukemia. We collected RNA sequencing (RNA-seq) data of human CLL, ALL samples, and normal peripheral blood CD19+ B cells as well as thymus samples, and analyzed similarities and differences between their transcriptomes using Cuffdiff2, DESeq, and edgeR. Compared with the RNA-seq data of normal peripheral blood CD19+ B cells and thymus samples, there were a large number of DEGs in ALL and CLL. DEGs in ALL and CLL not only have their distinguished features but also have a similar pattern. To figure out the common DEGs between CLL and ALL, we further identified 26 overlapped genes between CLL and ALL, among which 10 genes showed similar expression variation profiles whereas 16 genes showed opposite variation. The expression levels of 10 genes (SCML4, TNF-α, CD1C, FGFR1, MYO7B, DUSP1, PAP1GAP, MAN1C1, SLFN5, and CD8A) among the 26 genes were further confirmed by experiments, which was consistent with the results obtained by analyzing the RNA-seq data. The current study contributes to better understanding the pathophysiology of leukemia and unearthing novel potential prognostic markers and therapeutic targets of leukemia. CI - © 2019 Wiley Periodicals, Inc. FAU - Zhang, Suwei AU - Zhang S AD - Department of Clinical Laboratory, Shantou Central Hospital, Shantou, Guangdong, China. FAU - Zhang, Qiaoxin AU - Zhang Q AD - Department of Clinical Laboratory, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. FAU - Yin, Jun AU - Yin J AD - Department of Clinical Laboratory, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. FAU - Wu, Xianheng AU - Wu X AUID- ORCID: 0000-0003-2762-5863 AD - Department of Radiology, Shantou Central Hospital, Shantou, Guangdong, China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20190513 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Antigens, CD19) RN - 0 (CD19 molecule, human) SB - IM MH - Antigens, CD19/metabolism MH - B-Lymphocytes/chemistry MH - Computational Biology/*methods MH - Gene Expression Profiling/methods MH - Gene Expression Regulation, Leukemic MH - *Gene Regulatory Networks MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics MH - Protein Interaction Maps MH - Sequence Analysis, RNA MH - Thymus Gland/chemistry OTO - NOTNLM OT - *acute lymphoblastic leukemia OT - *chronic lymphocytic leukemia OT - *differentially expressed genes OT - *leukemia EDAT- 2019/05/14 06:00 MHDA- 2020/08/18 06:00 CRDT- 2019/05/14 06:00 PHST- 2018/11/06 00:00 [received] PHST- 2019/02/20 00:00 [revised] PHST- 2019/02/28 00:00 [accepted] PHST- 2019/05/14 06:00 [pubmed] PHST- 2020/08/18 06:00 [medline] PHST- 2019/05/14 06:00 [entrez] AID - 10.1002/jcb.28876 [doi] PST - ppublish SO - J Cell Biochem. 2019 Sep;120(9):15980-15988. doi: 10.1002/jcb.28876. Epub 2019 May 13. PMID- 31060831 OWN - NLM STAT- MEDLINE DCOM- 20200804 LR - 20200804 IS - 2405-4577 (Electronic) IS - 2405-4577 (Linking) VI - 31 DP - 2019 Jun TI - Is there a relationship between vitamin D nutritional status and metabolic syndrome in childhood acute lymphoblastic leukemia survivors? A PETALE study. PG - 28-32 LID - S2405-4577(19)30095-6 [pii] LID - 10.1016/j.clnesp.2019.03.006 [doi] AB - BACKGROUND: Treatment of childhood acute lymphoblastic leukemia (cALL) has reached unprecedented success leading to survival rates reaching 90%. This is regrettably linked to increased risk of developing long-term health-related sequels into early adulthood. OBJECTIVE: This study aims at assessing the relationship between the vitamin D status and metabolic biomarkers in PETALE, a well-characterized cohort of cALL survivors. RESULTS: We demonstrate that 15.9% of the study participants exhibited 3 or more metabolic syndrome (MetS) risk factors. We also show a direct relationship between s25OHD(3) and plasma HDL-Cholesterol concentrations in female but not male participants. CONCLUSION: Our data, from a metabolically well-described cohort, support a modest role for vitamin D in lipid metabolism in childhood leukemia survivors. The major outcome of this study is the strong association between HDL-Cholesterol concentration and s25OHD(3) only in female subjects, thereby conveying vitamin D a gender-specific cardio-protective effect. cALL survivors represent a population at higher risk for secondary diseases. For this reason thorough nutritional evaluation, including vitamin D should be part of the regular follow-up. CI - Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. FAU - Delvin, E AU - Delvin E AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Canada. Electronic address: delvine@sympatico.ca. FAU - Marcil, V AU - Marcil V AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Nutrition, Université de Montréal, Montréal, Canada. FAU - Alos, N AU - Alos N AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Pediatrics, Université de Montréal, Montréal, Canada. FAU - Laverdière, C AU - Laverdière C AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Pediatrics, Université de Montréal, Montréal, Canada. FAU - Sinnett, D AU - Sinnett D AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Pediatrics, Université de Montréal, Montréal, Canada. FAU - Krajinovic, M AU - Krajinovic M AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Pediatrics, Université de Montréal, Montréal, Canada. FAU - Bélanger, V AU - Bélanger V AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Nutrition, Université de Montréal, Montréal, Canada. FAU - Drouin, S AU - Drouin S AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada. FAU - Nyalendo, C AU - Nyalendo C AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Clinical Biochemistry, Sainte-Justine UHC, Université de Montréal, Montréal, Canada. FAU - Levy, E AU - Levy E AD - Sainte-Justine UHC Research Centre, Université de Montréal, Montréal, Canada; Department of Nutrition, Université de Montréal, Montréal, Canada. Electronic address: emile.levy@recherche-ste-justine.qc.ca. LA - eng GR - CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190402 PL - England TA - Clin Nutr ESPEN JT - Clinical nutrition ESPEN JID - 101654592 RN - 0 (Cholesterol, HDL) RN - 0 (Lipids) RN - 1406-16-2 (Vitamin D) RN - P6YZ13C99Q (Calcifediol) SB - IM MH - Adolescent MH - Adult MH - Calcifediol/blood MH - Cholesterol, HDL/blood MH - Cohort Studies MH - Female MH - Humans MH - Insulin Resistance MH - Lipids/blood MH - Male MH - Metabolic Syndrome/*complications MH - Nutrition Therapy MH - *Nutritional Status MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*complications MH - Risk Factors MH - Survivors MH - Vitamin D/*blood MH - Young Adult OTO - NOTNLM OT - *25-hydroxyvitamin D(3) OT - *Acute lymphoblastic leukemia OT - *Insulin resistance OT - *Lipids OT - *Metabolic syndrome OT - *Vitamin D EDAT- 2019/05/08 06:00 MHDA- 2020/08/05 06:00 CRDT- 2019/05/08 06:00 PHST- 2019/03/15 00:00 [received] PHST- 2019/03/18 00:00 [accepted] PHST- 2019/05/08 06:00 [entrez] PHST- 2019/05/08 06:00 [pubmed] PHST- 2020/08/05 06:00 [medline] AID - S2405-4577(19)30095-6 [pii] AID - 10.1016/j.clnesp.2019.03.006 [doi] PST - ppublish SO - Clin Nutr ESPEN. 2019 Jun;31:28-32. doi: 10.1016/j.clnesp.2019.03.006. Epub 2019 Apr 2. PMID- 31039409 OWN - NLM STAT- MEDLINE DCOM- 20200729 LR - 20200729 IS - 1523-6536 (Electronic) IS - 1083-8791 (Linking) VI - 25 IP - 9 DP - 2019 Sep TI - Outcomes of Allogeneic Stem Cell Transplantation after Inotuzumab Ozogamicin Treatment for Relapsed or Refractory Acute Lymphoblastic Leukemia. PG - 1720-1729 LID - S1083-8791(19)30267-8 [pii] LID - 10.1016/j.bbmt.2019.04.020 [doi] AB - Attaining complete remission of acute lymphoblastic leukemia (ALL) before hematopoietic stem cell transplantation (HSCT) correlates with better post-transplant outcomes. Inotuzumab ozogamicin (InO), an anti-CD22 antibody conjugated to calicheamicin, has shown significantly higher rates of remission, minimal residual disease negativity, and HSCT versus standard chemotherapy in treating relapsed/refractory (R/R) ALL. We investigated the role of previous transplant and proceeding directly to HSCT after remission as factors in determining post-transplant survival in the setting of InO treatment for R/R ALL. The analyzed population comprised InO-treated patients who proceeded to allogeneic HSCT in 2 clinical trials (phase 1/2: NCT01363297 and phase 3: NCT01564784). Overall survival (OS) was defined as time from HSCT to death (any cause). Of 236 InO-treated patients, 101 (43%) proceeded to allogeneic HSCT and were included in this analysis. Most received InO as first salvage (62%); 85% had no previous HSCT. Median (95% confidence interval [CI]) post-transplant OS was 9.2 months (5.1, not evaluable) with 2-year survival probability (95% CI) of 41% (32% to 51%). In first-HSCT patients (n = 86), median (95% CI) post-transplant OS was 11.8 months (5.9, not evaluable) with 2-year survival probability (95% CI) of 46% (35% to 56%); some patients relapsed and needed additional treatment before HSCT (n = 28). Those who went directly to first HSCT upon remission with no additional salvage/induction treatment (n = 73) fared best: median post-transplant OS was not reached with a 2-year survival probability (95% CI) of 51% (39% to 62%). In patients with R/R ALL, InO followed by allogeneic HSCT provided an optimal long-term survival benefit among those with no previous HSCT who went directly to transplant after remission. CI - Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Marks, David I AU - Marks DI AD - Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Trust, Bristol, United Kingdom. Electronic address: David.Marks@UHBristol.nhs.uk. FAU - Kebriaei, Partow AU - Kebriaei P AD - Department of Stem Cell Transplantation and Cellular Therapy and Department of Leukemia, MD Anderson Cancer Center, Houston, Texas. FAU - Stelljes, Matthias AU - Stelljes M AD - Department of Medicine/Hematology and Oncology, University of Muenster, Münster, Münster, Germany. FAU - Gökbuget, Nicola AU - Gökbuget N AD - Department of Medicine II, Department of Hematology/Oncology, Goethe University Hospital, Frankfurt, Germany. FAU - Kantarjian, Hagop AU - Kantarjian H AD - Department of Stem Cell Transplantation and Cellular Therapy and Department of Leukemia, MD Anderson Cancer Center, Houston, Texas. FAU - Advani, Anjali S AU - Advani AS AD - Division of Hematology/Oncology, Cleveland Clinic, Cleveland, Ohio. FAU - Merchant, Akil AU - Merchant A AD - Cedars-Sinai Medical Center, Los Angeles, California. FAU - Stock, Wendy AU - Stock W AD - Section of Hematology/Oncology, Department of Medicine, and University of Chicago Comprehensive Cancer Center, University of Chicago, Chicago, Illinois. FAU - Cassaday, Ryan D AU - Cassaday RD AD - Division of Hematology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. FAU - Wang, Tao AU - Wang T AD - Pfizer, Inc, Groton, Connecticut. FAU - Zhang, Hui AU - Zhang H AD - Pfizer, Inc, Shanghai, China. FAU - Loberiza, Fausto AU - Loberiza F AD - Pfizer, Inc, New York, New York. FAU - Vandendries, Erik AU - Vandendries E AD - Pfizer, Inc, Cambridge, Massachusetts. FAU - DeAngelo, Daniel J AU - DeAngelo DJ AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190427 PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - P93RUU11P7 (Inotuzumab Ozogamicin) SB - IM CIN - Biol Blood Marrow Transplant. 2019 Sep;25(9):e273-e274. PMID: 31260801 MH - Adult MH - Aged MH - Allografts MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Inotuzumab Ozogamicin/*administration & dosage MH - Male MH - Middle Aged MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/therapy MH - Recurrence MH - Survival Rate OTO - NOTNLM OT - *Allogeneic transplantation OT - *Hematopoietic stem cell transplantation OT - *Inotuzumab ozogamicin OT - *Relapsed or refractory acute lymphoblastic leukemia EDAT- 2019/05/01 06:00 MHDA- 2020/07/30 06:00 CRDT- 2019/05/01 06:00 PHST- 2019/02/12 00:00 [received] PHST- 2019/04/19 00:00 [revised] PHST- 2019/04/22 00:00 [accepted] PHST- 2019/05/01 06:00 [pubmed] PHST- 2020/07/30 06:00 [medline] PHST- 2019/05/01 06:00 [entrez] AID - S1083-8791(19)30267-8 [pii] AID - 10.1016/j.bbmt.2019.04.020 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2019 Sep;25(9):1720-1729. doi: 10.1016/j.bbmt.2019.04.020. Epub 2019 Apr 27. PMID- 30982165 OWN - NLM STAT- MEDLINE DCOM- 20200724 LR - 20200724 IS - 1179-2027 (Electronic) IS - 1170-7690 (Linking) VI - 37 IP - 10 DP - 2019 Oct TI - Tisagenlecleucel for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukaemia in People Aged up to 25 Years: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PG - 1209-1217 LID - 10.1007/s40273-019-00799-0 [doi] AB - As part of the National Institute for Health and Care Excellence's (NICE's) Single Technology Appraisal (STA) process, Novartis submitted evidence on the clinical effectiveness and cost-effectiveness of tisagenlecleucel for treating paediatric and young adult patients (under the age of 25 years) with relapsed or refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL). This article presents a summary of the Evidence Review Group's (ERG's) independent review of the evidence submission, the committee's deliberations, and the subsequent development of NICE guidance for the use of tisagenlecleucel on the National Health Service (NHS) in England. Tisagenlecleucel is a chimeric antigen receptor-modified T-cell (CAR-T) product, the first of this emerging therapeutic class to be considered by NICE in this indication. The company's evidence submission was based upon three single-arm, phase II studies: ELIANA, ENSIGN, and B2101J. These trials demonstrated a beneficial effect of tisagenlecleucel, with significant extensions in event-free survival (EFS) and overall survival (OS) compared to historical control datasets on blinatumomab and salvage chemotherapy. Adverse events were common; 77% of patients suffered from cytokine release syndrome (CRS), 56% of whom required intensive care unit-level care. The ERG did not consider clofarabine monotherapy an appropriate proxy for salvage chemotherapy. The company presented a hybrid cost-effectiveness model, combining a decision tree and three-state partitioned survival model structure. The majority of quality-adjusted life-years (QALYs) gained were generated through additional life-years in the extrapolated 'long-term survival' phase of the model, where patients were assumed to be 'cured'. The ERG considered the results to be subject to substantial uncertainty, due in part to immature trial data, unresolved long-term treatment effects, and a lack of appropriate comparator data. The ERG implemented a number of changes to the company's model in an alternative base case, producing deterministic incremental cost-effectiveness ratios (ICERs) of £45,397 per QALY gained versus salvage chemotherapy, and £27,732 versus blinatumomab. The probabilistic model produced ICERs of £48,265 per QALY gained versus salvage chemotherapy, and £29,501 versus blinatumomab. The committee considered the ERG's analysis to be most closely aligned with their preferred assumptions, and did not consider tisagenlecleucel to meet both of the end-of-life (EoL) criteria. In recognition of the innovative nature of tisagenlecleucel, and the present immaturity of ongoing clinical trials, the committee considered further data collection would be valuable in resolving uncertainties around OS, the technology's novel mechanism of action, and the management of CRS and B-cell aplasia. The committee therefore recommended tisagenlecleucel for use in the Cancer Drugs Fund (CDF) until the conclusion of the ELIANA study (June 2023). This appraisal highlighted the difficulty of interpreting EoL criteria in the context of curative therapies and the valuation of cure versus extension of life. Further clarification of NICE's position in these situations may be necessary to ensure consistency and equity in their decision-making. FAU - Walton, Matthew AU - Walton M AUID- ORCID: 0000-0003-1932-3689 AD - Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK. matthew.walton@york.ac.uk. FAU - Sharif, Sahar AU - Sharif S AD - Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK. FAU - Simmonds, Mark AU - Simmonds M AD - Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK. FAU - Claxton, Lindsay AU - Claxton L AD - Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK. FAU - Hodgson, Robert AU - Hodgson R AD - Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK. LA - eng GR - 17/141/10/DH_/Department of Health/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - New Zealand TA - Pharmacoeconomics JT - PharmacoEconomics JID - 9212404 RN - 0 (Antineoplastic Agents) RN - 0 (Receptors, Antigen, T-Cell) RN - Q6C9WHR03O (tisagenlecleucel) SB - T MH - Antineoplastic Agents/*administration & dosage/economics MH - Child MH - Cost-Benefit Analysis MH - Humans MH - Models, Economic MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/economics MH - Quality-Adjusted Life Years MH - Receptors, Antigen, T-Cell/*administration & dosage MH - Survival Analysis MH - Technology Assessment, Biomedical MH - Young Adult EDAT- 2019/04/15 06:00 MHDA- 2020/07/25 06:00 CRDT- 2019/04/15 06:00 PHST- 2019/04/15 06:00 [pubmed] PHST- 2020/07/25 06:00 [medline] PHST- 2019/04/15 06:00 [entrez] AID - 10.1007/s40273-019-00799-0 [pii] AID - 10.1007/s40273-019-00799-0 [doi] PST - ppublish SO - Pharmacoeconomics. 2019 Oct;37(10):1209-1217. doi: 10.1007/s40273-019-00799-0. PMID- 30947585 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20200821 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 60 IP - 9 DP - 2019 Sep TI - Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia. PG - 2214-2222 LID - 10.1080/10428194.2019.1576872 [doi] AB - Outcomes for adults with relapsed/refractory acute lymphoblastic leukemia (ALL) are poor with chemotherapy, particularly in later salvage. The TOWER study examined survival, remission, bridge to allogeneic hematopoietic stem cell transplantation (HSCT), and safety with blinatumomab versus chemotherapy. This report examined outcomes separately for study treatment as first or later salvage. Adults with Philadelphia chromosome-negative B-cell precursor ALL relapsed/refractory to chemotherapy were randomly assigned 2:1 to receive blinatumomab by continuous infusion for 4 weeks in 6-week cycles, or standard salvage chemotherapy. Overall survival for blinatumomab versus chemotherapy was higher both in first salvage and in later salvage. Safety was similar between patients in first salvage and those in later salvage. Blinatumomab as later salvage was associated with higher complete remission rates and served as a bridge to allogeneic HSCT, supporting the use of blinatumomab in both settings. This study is registered at www.clinicaltrials.gov as #NCT02013167. FAU - Dombret, Hervé AU - Dombret H AD - Department of Hematology, Hôpital Saint-Louis (Assistance Publique - Hôpitaux de Paris) and University Paris Diderot , Paris , France. FAU - Topp, Max S AU - Topp MS AD - Klinik und Poliklinik II, Universitätsklinikum Würzburg , Würzburg , Germany. FAU - Schuh, Andre C AU - Schuh AC AD - Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network , Toronto , Canada. FAU - Wei, Andrew H AU - Wei AH AD - Department of Haematology, Alfred Hospital and Monash University , Melbourne , Australia. FAU - Durrant, Simon AU - Durrant S AD - Bone Marrow Transplant Unit, Royal Brisbane Hospital , Herston , Australia. FAU - Bacon, Christopher Larry AU - Bacon CL AD - Haematology Department, St. James's Hospital , Dublin , Ireland. FAU - Tran, Qui AU - Tran Q AD - Amgen Inc , Thousand Oaks , CA , USA. FAU - Zimmerman, Zachary AU - Zimmerman Z AD - Amgen Inc , Thousand Oaks , CA , USA. FAU - Kantarjian, Hagop AU - Kantarjian H AD - Department of Leukemia, University of Texas M.D. Anderson Cancer Center , Houston , TX , USA. LA - eng SI - ClinicalTrials.gov/NCT02013167 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190405 PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antibodies, Bispecific) RN - 0 (Antineoplastic Agents) RN - 4FR53SIF3A (blinatumomab) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Bispecific/*administration & dosage/adverse effects MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Chemotherapy, Adjuvant/methods MH - Drug Administration Schedule MH - Drug Resistance, Neoplasm MH - Female MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Infusions, Intravenous MH - Male MH - Middle Aged MH - Neoadjuvant Therapy/adverse effects/methods MH - Neoplasm Recurrence, Local/pathology/*therapy MH - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality/pathology/*therapy MH - Progression-Free Survival MH - Remission Induction/methods MH - Salvage Therapy/adverse effects/*methods MH - Young Adult OTO - NOTNLM OT - *Acute lymphoblastic leukemia OT - *blinatumomab OT - *chemotherapy OT - *salvage OT - *transplantation EDAT- 2019/04/06 06:00 MHDA- 2020/08/22 06:00 CRDT- 2019/04/06 06:00 PHST- 2019/04/06 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2019/04/06 06:00 [entrez] AID - 10.1080/10428194.2019.1576872 [doi] PST - ppublish SO - Leuk Lymphoma. 2019 Sep;60(9):2214-2222. doi: 10.1080/10428194.2019.1576872. Epub 2019 Apr 5. PMID- 30940639 OWN - NLM STAT- MEDLINE DCOM- 20200723 LR - 20200723 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 3 IP - 7 DP - 2019 Apr 9 TI - Germline deletion of ETV6 in familial acute lymphoblastic leukemia. PG - 1039-1046 LID - 10.1182/bloodadvances.2018030635 [doi] AB - Recent studies have identified germline mutations in TP53, PAX5, ETV6, and IKZF1 in kindreds with familial acute lymphoblastic leukemia (ALL), but the genetic basis of ALL in many kindreds is unknown despite mutational analysis of the exome. Here, we report a germline deletion of ETV6 identified by linkage and structural variant analysis of whole-genome sequencing data segregating in a kindred with thrombocytopenia, B-progenitor acute lymphoblastic leukemia, and diffuse large B-cell lymphoma. The 75-nt deletion removed the ETV6 exon 7 splice acceptor, resulting in exon skipping and protein truncation. The ETV6 deletion was also identified by optimal structural variant analysis of exome sequencing data. These findings identify a new mechanism of germline predisposition in ALL and implicate ETV6 germline variation in predisposition to lymphoma. Importantly, these data highlight the importance of germline structural variant analysis in the search for germline variants predisposing to familial leukemia. CI - © 2019 by The American Society of Hematology. FAU - Rampersaud, Evadnie AU - Rampersaud E AUID- ORCID: 0000-0001-5195-5366 AD - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN. FAU - Ziegler, David S AU - Ziegler DS AUID- ORCID: 0000-0001-7451-7916 AD - Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia. AD - Childrens Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia. FAU - Iacobucci, Ilaria AU - Iacobucci I AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis TN. FAU - Payne-Turner, Debbie AU - Payne-Turner D AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis TN. FAU - Churchman, Michelle L AU - Churchman ML AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis TN. FAU - Schrader, Kasmintan A AU - Schrader KA AD - Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada. AD - Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. FAU - Joseph, Vijai AU - Joseph V AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. AD - Sloan Kettering Institute, New York, NY. FAU - Offit, Kenneth AU - Offit K AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. FAU - Tucker, Katherine AU - Tucker K AD - Hereditary Cancer Centre, Prince of Wales Hospital, Sydney, NSW, Australia. FAU - Sutton, Rosemary AU - Sutton R AD - Childrens Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia. FAU - Warby, Meera AU - Warby M AD - Hereditary Cancer Centre, Prince of Wales Hospital, Sydney, NSW, Australia. AD - Prince of Wales Clinical School University of NSW Australia, Sydney, NSW, Australia. FAU - Chenevix-Trench, Georgia AU - Chenevix-Trench G AUID- ORCID: 0000-0002-1878-2587 AD - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. FAU - Huntsman, David G AU - Huntsman DG AD - Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada. AD - Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; and. FAU - Tsoli, Maria AU - Tsoli M AD - Childrens Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia. FAU - Mead, R Scott AU - Mead RS AD - South Eastern Area Laboratory Service, Prince of Wales Hospital, Randwick, NSW, Australia. FAU - Qu, Chunxu AU - Qu C AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis TN. FAU - Leventaki, Vasiliki AU - Leventaki V AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis TN. FAU - Wu, Gang AU - Wu G AD - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN. FAU - Mullighan, Charles G AU - Mullighan CG AUID- ORCID: 0000-0002-1871-1850 AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis TN. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - P30 CA021765/CA/NCI NIH HHS/United States GR - R35 CA197695/CA/NCI NIH HHS/United States GR - CIHR/Canada PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (ETS translocation variant 6 protein) RN - 0 (Proto-Oncogene Proteins c-ets) RN - 0 (Repressor Proteins) SB - IM MH - DNA Mutational Analysis MH - Exome/genetics MH - Family MH - Genetic Predisposition to Disease MH - *Germ-Line Mutation MH - Humans MH - Lymphoma, Large B-Cell, Diffuse/genetics MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics MH - Proto-Oncogene Proteins c-ets/*genetics MH - Repressor Proteins/*genetics MH - *Sequence Deletion MH - Thrombocytopenia/genetics PMC - PMC6457220 COIS- Conflict-of-interest disclosure: C.G.M. has received consulting fees and travel funding from Amgen and Pfizer and research funding from AbbVie, Loxo Oncology, and Pfizer. The content of these activities and research is unrelated to the content of this manuscript. The remaining authors declare no competing financial interests. EDAT- 2019/04/04 06:00 MHDA- 2020/07/24 06:00 CRDT- 2019/04/04 06:00 PHST- 2018/12/27 00:00 [received] PHST- 2019/02/23 00:00 [accepted] PHST- 2019/04/04 06:00 [entrez] PHST- 2019/04/04 06:00 [pubmed] PHST- 2020/07/24 06:00 [medline] AID - bloodadvances.2018030635 [pii] AID - 2018/030635 [pii] AID - 10.1182/bloodadvances.2018030635 [doi] PST - ppublish SO - Blood Adv. 2019 Apr 9;3(7):1039-1046. doi: 10.1182/bloodadvances.2018030635. PMID- 30848084 OWN - NLM STAT- MEDLINE DCOM- 20200811 LR - 20200811 IS - 2163-8306 (Electronic) IS - 2163-8306 (Linking) VI - 8 IP - 5 DP - 2019 May TI - Tisagenlecleucel Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells. PG - 285-295 LID - 10.1002/psp4.12388 [doi] AB - Tisagenlecleucel is a chimeric antigen receptor-T cell therapy that facilitates the killing of CD19(+) B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion. The doubling time, initial decline half-life, and terminal half-life for tisagenlecleucel were 0.78, 4.3, and 220 days, respectively. No impact of tocilizumab or corticosteroids on the expansion rate was observed. This work represents the first mixed-effect model-based analysis of chimeric antigen receptor-T cell therapy and may be clinically impactful as future studies examine prophylactic interventions in patients at risk of higher grade cytokine release syndrome and the effects of these interventions on chimeric antigen receptor-T cell expansion. CI - © 2019 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. FAU - Stein, Andrew M AU - Stein AM AD - Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA. FAU - Grupp, Stephan A AU - Grupp SA AD - Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. FAU - Levine, John E AU - Levine JE AD - University of Michigan, Ann Arbor, Michigan, USA. AD - Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Laetsch, Theodore W AU - Laetsch TW AD - Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas, USA. AD - Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health, Dallas, Texas, USA. FAU - Pulsipher, Michael A AU - Pulsipher MA AD - Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, California, USA. FAU - Boyer, Michael W AU - Boyer MW AD - Department of Pediatrics and Internal Medicine, University of Utah, Salt Lake City, Utah, USA. FAU - August, Keith J AU - August KJ AUID- ORCID: 0000-0002-5690-0855 AD - Children's Mercy Hospital Kansas City, Kansas City, Missouri, USA. FAU - Levine, Bruce L AU - Levine BL AD - Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Tomassian, Lori AU - Tomassian L AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Shah, Sweta AU - Shah S AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Leung, Mimi AU - Leung M AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Huang, Pai-Hsi AU - Huang PH AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Awasthi, Rakesh AU - Awasthi R AD - Novartis Institutes for BioMedical Research, East Hanover, New Jersey, USA. FAU - Mueller, Karen Thudium AU - Mueller KT AD - Novartis Institutes for BioMedical Research, East Hanover, New Jersey, USA. FAU - Wood, Patricia A AU - Wood PA AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - June, Carl H AU - June CH AD - Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - P01 CA214278/CA/NCI NIH HHS/United States GR - P30 CA016520/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190307 TA - CPT Pharmacometrics Syst Pharmacol JT - CPT: pharmacometrics & systems pharmacology JID - 101580011 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Receptors, Antigen, T-Cell) RN - I031V2H011 (tocilizumab) RN - Q6C9WHR03O (tisagenlecleucel) SB - IM MH - Adolescent MH - Adult MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Child MH - Child, Preschool MH - Clinical Trials, Phase II as Topic MH - Female MH - Half-Life MH - Humans MH - Immunotherapy, Adoptive MH - Lymphoma, Large B-Cell, Diffuse/*therapy MH - Male MH - Models, Theoretical MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology/*therapy MH - Receptors, Antigen, T-Cell/*administration & dosage MH - Young Adult PMC - PMC6539725 COIS- A.M.S. is an employee of Novartis Institutes for BioMedical Research and owns equity in Novartis Pharmaceuticals Corporation. S.A.G. received consultancy fees from Novartis Pharmaceuticals Corporation, Jazz Pharmaceuticals, Adaptimmune and research support from Novartis Pharmaceuticals Corporation. J.E.L. received consultancy fees from Novartis Pharmaceuticals Corporation, Jazz Pharmaceuticals, Bluebird Bio, and Therakos, Inc. and holds patents, royalties, or intellectual property with Viracor. T.W.L. received consultancy fees from Novartis Pharmaceuticals Corporation, Loxo Oncology, and Eli Lilly and received researching funding from Pfizer. M.A.P. received consultancy fees from Novartis Pharmaceuticals Corporation and Jazz Pharmaceuticals and received travel accommodations or expenses from Medac and research funding from Adaptive Biotechnologies. M.W.B. received honoraria from Novartis Pharmaceuticals Corporation. K.J.A. participated in a speaker bureau for and received travel accommodations and expenses from Novartis Pharmaceuticals Corporation. B.L.L. received consultancy fees from GE Health and Brammer Bio, has patents and royalties with and received research funding from Novartis Pharmaceuticals Corporation, and holds equity ownership in and received research funding from Tmunity Therapeutics. L.T., S.S., M.L., and P.H.H. are employees of Novartis Pharmaceuticals Corporation and own equity in Novartis Pharmaceuticals Corporation. R.A. is an employee of Novartis Institutes for BioMedical Research and holds stock or equity ownership in Exelixis, Cara Therapeutics, Ultragenyx, and Aeterna Zentari. K.T.M. is an employee of Novartis Institutes for BioMedical Research and owns equity in Novartis Pharmaceuticals Corporation and has patents pending related to the submitted work. P.A.W. is a former employee of Novartis Pharmaceuticals Corporation and owns equity in Novartis Pharmaceuticals Corporation. C.H.J. received research support from Novartis Pharmaceuticals Corporation, received honoraria from and is a member on the board of directors or advisory committee for Western Institutional Review Board (WIRB) Copernicus Group and Celldex, owns equity in and is a member on a board of directors or advisory committee for Immune Design, has patents and royalties with Novartis Pharmaceuticals Corporation, and received research funding from Tmunity Therapeutics. EDAT- 2019/03/09 06:00 MHDA- 2020/08/12 06:00 CRDT- 2019/03/09 06:00 PHST- 2018/07/09 00:00 [received] PHST- 2019/01/17 00:00 [accepted] PHST- 2019/03/09 06:00 [pubmed] PHST- 2020/08/12 06:00 [medline] PHST- 2019/03/09 06:00 [entrez] AID - PSP412388 [pii] AID - 10.1002/psp4.12388 [doi] PST - ppublish SO - CPT Pharmacometrics Syst Pharmacol. 2019 May;8(5):285-295. doi: 10.1002/psp4.12388. Epub 2019 Mar 7. PMID- 30721104 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20200821 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 60 IP - 9 DP - 2019 Sep TI - Asparaginase activity monitoring experience from the Maritimes, Canada. PG - 2312-2315 LID - 10.1080/10428194.2019.1571196 [doi] FAU - Pike, Meghan AU - Pike M AD - Department of Pediatrics, Dalhousie University/IWK Health Centre , Halifax , Nova Scotia , Canada. FAU - Kulkarni, Ketan AU - Kulkarni K AD - Department of Pediatrics/Division of Pediatric Hematology-Oncology, Dalhousie University/IWK Health Centre , Halifax , Nova Scotia , Canada. FAU - MacDonald, Tamara AU - MacDonald T AD - Department of Pharmacy, Faculty of Health Professions, Dalhousie University/IWK Health Centre , Halifax , Nova Scotia , Canada. LA - eng PT - Letter DEP - 20190205 PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antineoplastic Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 7D96IR0PPM (pegaspargase) RN - EC 3.5.1.1 (Asparaginase) SB - IM MH - Adolescent MH - Antineoplastic Agents/*blood/therapeutic use MH - Asparaginase/*blood/therapeutic use MH - Canada MH - Child MH - Child, Preschool MH - Drug Monitoring/methods/*statistics & numerical data MH - Female MH - Humans MH - Male MH - Polyethylene Glycols/therapeutic use MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood/*drug therapy MH - Prospective Studies MH - Remission Induction/methods EDAT- 2019/02/06 06:00 MHDA- 2020/08/22 06:00 CRDT- 2019/02/06 06:00 PHST- 2019/02/06 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2019/02/06 06:00 [entrez] AID - 10.1080/10428194.2019.1571196 [doi] PST - ppublish SO - Leuk Lymphoma. 2019 Sep;60(9):2312-2315. doi: 10.1080/10428194.2019.1571196. Epub 2019 Feb 5. PMID- 30632830 OWN - NLM STAT- MEDLINE DCOM- 20200811 LR - 20200811 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 60 IP - 8 DP - 2019 Aug TI - Treatment patterns, survival, and hospitalization in adult patients with acute lymphoblastic leukemia: an observational cohort study using SEER Medicare data. PG - 2015-2024 LID - 10.1080/10428194.2018.1555329 [doi] AB - There is little evidence about whether additional risk stratification for adult patients with acute lymphoblastic leukemia age 65 and older is warranted. Using the Surveillance, Epidemiology, and End Results data linked to Medicare claims, we examined the effects of age, comorbid conditions, and mobility limitations on treatment and survival in a cohort of 795 patients diagnosed with ALL between 1 January 2000 and 31 December 2009. In the cohort, 54% received chemotherapy within the first 90 days, of whom 74% were hospitalized during the first chemotherapy administration. Unadjusted median survival was 172 days (95% CI = 244-379) for the overall cohort, 325 days (95% CI = 244-379) for those age 65-69, but only 59 days (95% CI = 45-76) for those age ≥80. In multivariate analyses, older age groups (70-74, 75-79, and ≥80) and comorbidity score ≥2 were independently associated with poorer survival. Treatment and outcomes vary considerably among subgroups of older patients suggesting that further risk stratification may be useful. FAU - Danese, Mark D AU - Danese MD AUID- ORCID: 0000-0002-7068-9603 AD - a Outcomes Insights, Inc , Westlake Village , CA , USA. FAU - Katz, Aaron AU - Katz A AD - b Amgen, Inc , Thousand Oaks , CA , USA. FAU - Cetin, Karynsa AU - Cetin K AD - b Amgen, Inc , Thousand Oaks , CA , USA. FAU - Chia, Victoria AU - Chia V AD - b Amgen, Inc , Thousand Oaks , CA , USA. FAU - Gleeson, Michelle L AU - Gleeson ML AD - a Outcomes Insights, Inc , Westlake Village , CA , USA. FAU - Kelsh, Michael AU - Kelsh M AD - b Amgen, Inc , Thousand Oaks , CA , USA. FAU - Griffiths, Robert I AU - Griffiths RI AD - a Outcomes Insights, Inc , Westlake Village , CA , USA. AD - c Nuffield Department of Primary Care Health Sciences , University of Oxford , Oxford , UK. AD - d Johns Hopkins University School of Medicine , Baltimore , MD , USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190111 PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 SB - IM MH - Adult MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Cohort Studies MH - Comorbidity MH - Female MH - Health Care Surveys MH - *Hospitalization MH - Humans MH - Male MH - Medicare MH - Middle Aged MH - *Practice Patterns, Physicians' MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*epidemiology/mortality/therapy MH - Prognosis MH - Proportional Hazards Models MH - SEER Program MH - Treatment Outcome MH - United States/epidemiology MH - Young Adult OTO - NOTNLM OT - *Leukemia OT - *adult OT - *comorbidity OT - *health status OT - *hospitalization OT - *mortality OT - *survival OT - *treatment EDAT- 2019/01/12 06:00 MHDA- 2020/08/12 06:00 CRDT- 2019/01/12 06:00 PHST- 2019/01/12 06:00 [pubmed] PHST- 2020/08/12 06:00 [medline] PHST- 2019/01/12 06:00 [entrez] AID - 10.1080/10428194.2018.1555329 [doi] PST - ppublish SO - Leuk Lymphoma. 2019 Aug;60(8):2015-2024. doi: 10.1080/10428194.2018.1555329. Epub 2019 Jan 11. PMID- 30532056 OWN - NLM STAT- MEDLINE DCOM- 20200728 LR - 20200728 IS - 1476-5365 (Electronic) IS - 0268-3369 (Linking) VI - 54 IP - 7 DP - 2019 Jul TI - PAX5, NOTCH3, CBFB, and ACD drive an activated RAS pathway and monosomy 7 to B-ALL and AML in donor cell leukemia. PG - 1124-1128 LID - 10.1038/s41409-018-0419-7 [doi] FAU - Assi, Rita AU - Assi R AD - Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. FAU - Mahfouz, Rami AU - Mahfouz R AD - Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon. FAU - Owen, Renius AU - Owen R AD - Quest Diagnostics, Nichols Institute, San Juan Capistrano, CA, USA. FAU - Gunthorpe, Martha AU - Gunthorpe M AD - Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. FAU - Chehab, Farid F AU - Chehab FF AD - Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. FAU - Bazarbachi, Ali AU - Bazarbachi A AD - Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. bazarbac@aub.edu.lb. LA - eng PT - Clinical Trial PT - Letter DEP - 20181210 PL - England TA - Bone Marrow Transplant JT - Bone marrow transplantation JID - 8702459 RN - 0 (ACD protein, human) RN - 0 (CBFB protein, human) RN - 0 (Core Binding Factor beta Subunit) RN - 0 (NOTCH3 protein, human) RN - 0 (PAX5 Transcription Factor) RN - 0 (PAX5 protein, human) RN - 0 (Receptor, Notch3) RN - 0 (Telomere-Binding Proteins) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) RN - Chromosome 7, monosomy SB - IM MH - Adult MH - *Chromosome Deletion MH - Chromosomes, Human, Pair 7 MH - *Core Binding Factor beta Subunit/genetics/metabolism MH - Female MH - Humans MH - *Leukemia, Myeloid, Acute/genetics/metabolism MH - Male MH - Middle Aged MH - *PAX5 Transcription Factor/genetics/metabolism MH - *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics/metabolism MH - *Proto-Oncogene Proteins p21(ras)/genetics/metabolism MH - *Receptor, Notch3 MH - *Signal Transduction MH - *Telomere-Binding Proteins/genetics/metabolism EDAT- 2018/12/12 06:00 MHDA- 2020/07/29 06:00 CRDT- 2018/12/12 06:00 PHST- 2018/10/07 00:00 [received] PHST- 2018/11/22 00:00 [accepted] PHST- 2018/11/20 00:00 [revised] PHST- 2018/12/12 06:00 [pubmed] PHST- 2020/07/29 06:00 [medline] PHST- 2018/12/12 06:00 [entrez] AID - 10.1038/s41409-018-0419-7 [pii] AID - 10.1038/s41409-018-0419-7 [doi] PST - ppublish SO - Bone Marrow Transplant. 2019 Jul;54(7):1124-1128. doi: 10.1038/s41409-018-0419-7. Epub 2018 Dec 10. PMID- 30518980 OWN - NLM STAT- MEDLINE DCOM- 20200812 LR - 20200812 IS - 1476-5365 (Electronic) IS - 0268-3369 (Linking) VI - 54 IP - 8 DP - 2019 Aug TI - A retrospective comparison of allogenic and autologous chimeric antigen receptor T cell therapy targeting CD19 in patients with relapsed/refractory acute lymphoblastic leukemia. PG - 1208-1217 LID - 10.1038/s41409-018-0403-2 [doi] AB - The source of CAR T cells can be autologous (autoCAR) or allogeneic (alloCAR). The latter is seen in patients with a history of allogeneic hematopoietic stem cell transplantation, and can be either donor-derived (DD-alloCAR) or recipient-derived (RD-alloCAR). While autoCAR is activated by CAR only, alloCAR receives activation signals from both T-cell receptor (TCR) and CAR. As a result, the biological differences could impact clinical outcomes. We retrospectively reviewed 31 patients: 17 received autoCAR, 11 received RD-alloCAR, and 3 received DD-alloCAR. After a median follow-up of 9 months, CR rate was 88.2% (95% CI 63.6-98.5%) in autoCAR and 100% (95% CI 71.5-100%) in RD-alloCAR. The median peak expansion in the autoCAR was significantly higher than the RD-alloCAR group (p = 0.007). RD-alloCAR group had significantly less patients with severe CRS (Grade ≥ 3) than the autoCAR group (p = 0.049). Acute graft-versus-host disease (GVHD) occurred in 2 (18.2%) of RD-alloCAR patients and 1 (33.3%) of DD-alloCAR patients. Univariate subgroup analysis of alloCAR group showed the presence of cGVHD at the time of T-cell collection was significantly associated with less than 6-month relapses (p = 0.022). RD-alloCAR patients with or without cGVHD at PBMC collection did not differ regarding the peak CAR T-cell expansion, CRS grades and OS. FAU - Hu, Yongxian AU - Hu Y AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Wang, Jiasheng AU - Wang J AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Wei, Guoqing AU - Wei G AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Yu, Jian AU - Yu J AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Luo, Yi AU - Luo Y AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Shi, Jimin AU - Shi J AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Wu, Wenjun AU - Wu W AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Zhao, Kui AU - Zhao K AD - PETCT Center, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. FAU - Xiao, Lei AU - Xiao L AD - Innovative Cellular Therapeutics Co. Ltd, Shanghai, China. FAU - Zhang, Yanlei AU - Zhang Y AD - Shanghai YaKe Biotechnology Ltd, Shanghai, China. FAU - Wu, Zhao AU - Wu Z AD - Innovative Cellular Therapeutics Co. Ltd, Shanghai, China. FAU - Xu, Huijun AU - Xu H AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. FAU - Chang, Alex Hongsheng AU - Chang AH AD - Shanghai YaKe Biotechnology Ltd, Shanghai, China. FAU - Huang, He AU - Huang H AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. huanghe@zju.edu.cn. AD - Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang, China. huanghe@zju.edu.cn. AD - Institute of Hematology, Zhejiang University, Zhejiang, China. huanghe@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181205 PL - England TA - Bone Marrow Transplant JT - Bone marrow transplantation JID - 8702459 RN - 0 (Antigens, CD19) RN - 0 (Receptors, Chimeric Antigen) SB - IM MH - Antigens, CD19/*immunology MH - Female MH - Hematopoietic Stem Cell Transplantation/*methods MH - Humans MH - Male MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology MH - Receptors, Chimeric Antigen/*metabolism MH - Recurrence MH - Retrospective Studies MH - T-Lymphocytes/*immunology MH - Transplantation Conditioning/*methods MH - Transplantation, Homologous/*methods EDAT- 2018/12/07 06:00 MHDA- 2020/08/13 06:00 CRDT- 2018/12/07 06:00 PHST- 2018/10/03 00:00 [received] PHST- 2018/11/02 00:00 [accepted] PHST- 2018/10/30 00:00 [revised] PHST- 2018/12/07 06:00 [pubmed] PHST- 2020/08/13 06:00 [medline] PHST- 2018/12/07 06:00 [entrez] AID - 10.1038/s41409-018-0403-2 [pii] AID - 10.1038/s41409-018-0403-2 [doi] PST - ppublish SO - Bone Marrow Transplant. 2019 Aug;54(8):1208-1217. doi: 10.1038/s41409-018-0403-2. Epub 2018 Dec 5. PMID- 30279573 OWN - NLM STAT- MEDLINE DCOM- 20200728 LR - 20200728 IS - 1476-5365 (Electronic) IS - 0268-3369 (Print) IS - 0268-3369 (Linking) VI - 54 IP - 7 DP - 2019 Jul TI - Pre-transplant expressions of microRNAs, comorbidities, and post-transplant mortality. PG - 973-979 LID - 10.1038/s41409-018-0352-9 [doi] AB - We analyzed micro-RNAs (miRs) as possible diagnostic biomarkers for relevant comorbidities prior to and prognostic biomarkers for mortality following hematopoietic cell transplantation (HCT). A randomly selected group of patients (n = 36) were divided into low-risk (HCT-comorbidity index [HCT-CI] score of 0 and survived HCT) and high-risk (HCT-CI scores ≥ 4 and deceased after HCT) groups. There were 654 miRs tested and 19 met the pre-specified significance level of p < 0.1. In subsequent models, only eight miRs maintained statistical significance in regression models after adjusting for baseline demographic factors; miRs-374b and -454 were underexpressed, whereas miRs-142-3p, -191, -424, -590-3p, -29c, and -15b were overexpressed among high-risk patients relative to low-risk patients. Areas under the curve for these eight miRs ranged between 0.74 and 0.81, suggesting strong predictive capacity. Consideration of miRs may improve risk assessment of mortality and should be further explored in larger future prospective studies. FAU - Sorror, Mohamed L AU - Sorror ML AUID- ORCID: 0000-0001-5260-1981 AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. msorror@fredhutch.org. AD - University of Washington, Seattle, WA, USA. msorror@fredhutch.org. FAU - Gooley, Ted A AU - Gooley TA AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. AD - University of Washington, Seattle, WA, USA. FAU - Maclean, Kirsteen H AU - Maclean KH AD - NanoString Technologies, Seattle, WA, USA. FAU - Hubbard, Jesse AU - Hubbard J AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. FAU - Marcondes, Mario A AU - Marcondes MA AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. AD - University of Washington, Seattle, WA, USA. FAU - Torok-Storb, Beverly J AU - Torok-Storb BJ AD - Fred Hutchinson Cancer Research Center, Seattle, WA, USA. AD - University of Washington, Seattle, WA, USA. FAU - Tewari, Muneesh AU - Tewari M AD - University of Michigan, Ann Arbor, MI, USA. LA - eng GR - R00 HL088021/HL/NHLBI NIH HHS/United States GR - P30 DK056465/DK/NIDDK NIH HHS/United States GR - U01 HL099993/HL/NHLBI NIH HHS/United States GR - K99 HL088021/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181002 TA - Bone Marrow Transplant JT - Bone marrow transplantation JID - 8702459 RN - 0 (MicroRNAs) RN - 0 (RNA, Neoplasm) SB - IM MH - Adult MH - Aged MH - Allografts MH - Disease-Free Survival MH - Female MH - *Gene Expression Regulation, Leukemic MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - *Leukemia, Myeloid, Acute/metabolism/mortality/therapy MH - Male MH - MicroRNAs/*biosynthesis MH - Middle Aged MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism/mortality/therapy MH - Predictive Value of Tests MH - *Preoperative Period MH - RNA, Neoplasm/*biosynthesis MH - Retrospective Studies MH - Survival Rate PMC - PMC6445788 MID - NIHMS1506655 COIS- Conflict of interest: Dr. Maclean is employed by NanoString Technologies, which provided the assay to determine expressions of miRs. Dr. Sorror, Dr. Gooley, Mr. Hubbard, Dr. Marcondes, Dr. Torok-Storb, and Dr. Tewari declare no potential conflict of interest. Conflict of interest statement: Kirsteen H. Maclean is employed by NanoString Technologies, which provided the assay to determine expressions of miRs; otherwise, the authors have no competing interests. EDAT- 2018/10/04 06:00 MHDA- 2020/07/29 06:00 CRDT- 2018/10/04 06:00 PHST- 2018/03/23 00:00 [received] PHST- 2018/09/12 00:00 [accepted] PHST- 2018/08/29 00:00 [revised] PHST- 2018/10/04 06:00 [pubmed] PHST- 2020/07/29 06:00 [medline] PHST- 2018/10/04 06:00 [entrez] AID - 10.1038/s41409-018-0352-9 [pii] AID - 10.1038/s41409-018-0352-9 [doi] PST - ppublish SO - Bone Marrow Transplant. 2019 Jul;54(7):973-979. doi: 10.1038/s41409-018-0352-9. Epub 2018 Oct 2.