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Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study

A. Attarbaschi, A. Möricke, CJ. Harrison, G. Mann, A. Baruchel, B. De Moerloose, V. Conter, M. Devidas, S. Elitzur, G. Escherich, SP. Hunger, K. Horibe, A. Manabe, ML. Loh, R. Pieters, K. Schmiegelow, LB. Silverman, J. Stary, A. Vora, CH. Pui, M....

. 2023 ; 41 (7) : 1404-1422. [pub] 20221018

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural

Perzistentní odkaz   https://www.medvik.cz/link/bmc23004049

Grantová podpora
U10 CA180886 NCI NIH HHS - United States
U10 CA180899 NCI NIH HHS - United States

PURPOSE: We aimed to study prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/KMT2A rearrangements treated with chemotherapy regimens between 1995 and 2010. PATIENTS AND METHODS: Data were retrospectively retrieved from 629 patients with 11q23/KMT2A-rearranged ALL from 17 members of the Ponte-di-Legno Childhood ALL Working Group. Clinical and biologic characteristics, early response assessed by minimal residual disease at the end of induction (EOI) therapy, and allo-HSCT were analyzed for their impact on outcomes. RESULTS: A specific 11q23/KMT2A translocation partner gene was identified in 84.3% of patients, with the most frequent translocations being t(4;11)(q21;q23) (n = 273; 51.5%), t(11;19)(q23;p13.3) (n = 106; 20.0%), t(9;11)(p21_22;q23) (n = 76; 14.3%), t(6;11)(q27;q23) (n = 20; 3.8%), and t(10;11)(p12;q23) (n = 14; 2.6%); 41 patients (7.7%) had less frequently identified translocation partner genes. Patient characteristics and early response varied among subgroups, indicating large biologic heterogeneity and diversity in therapy sensitivity among 11q23/KMT2A-rearranged ALL. The EOI remission rate was 93.2%, and the 5-year event-free survival (EFS) for the entire cohort was 69.1% ± 1.9%, with a range from 41.7% ± 17.3% for patients with t(9;11)-positive T-ALL (n = 9) and 64.8% ± 3.0% for patients with t(4;11)-positive B-ALL (n = 266) to 91.2% ± 4.9% for patients with t(11;19)-positive T-ALL (n = 34). Low EOI minimal residual disease was associated with favorable EFS, and induction failure was particularly predictive of nonresponse to further therapy and relapse and poor EFS. In addition, EFS was not improved by allo-HSCT compared with chemotherapy only in patients with both t(4;11)-positive B-ALL (n = 64 v 51; P = .10) and 11q23/KMT2A-rearranged T-ALL (n = 16 v 10; P = .69). CONCLUSION: Compared with historical data, prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved, but allo-HSCT failed to affect outcome. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.

Ben Towne Center for Childhood Cancer Research Seattle Children's Research Institute Seattle WA

Boston Children's Hospital and Harvard Medical School Boston MA

Children's Hospital of Philadelphia Philadelphia PA

Christian Albrechts University Kiel and University Medical Center Schleswig Holstein Kiel Germany

Clinic of Paediatric Haematology and Oncology University Medical Centre Hamburg Eppendorf Hamburg Germany

Department of Global Pediatric Medicine St Jude Children's Research Hospital Memphis TN

Department of Pediatrics Seattle Children's Hospital University of Washington Seattle WA

Faculty of Medicine Institute of Clinical Medicine University of Copenhagen Copenhagen Denmark

Ghent University Hospital Ghent Belgium

Great Ormond Street Hospital London United Kingdom

Hokkaido University Graduate School of Medicine Sapporo Japan

Leukaemia Research Cytogenetics Group Translational and Clinical Research Institute Newcastle University Centre for Cancer Newcastle upon Tyne United Kingdom

Medical School Hannover Hannover Germany

National Hospital Organization Nagoya Medical Center Nagoya Japan

Princess Máxima Centre for Pediatric Oncology Utrecht the Netherlands

Rigshospitalet and University Hospital Copenhagen Copenhagen Denmark

Robert Debré University Hospital Université Paris Cité Paris France

Schneider Children's Medical Center Tel Aviv Israel

St Anna Children's Hospital and St Anna Children's Cancer Research Institute Medical University of Vienna Vienna Austria

St Jude Children's Research Hospital Memphis TN

Tel Aviv University Tel Aviv Israel

University Hospital Motol and Charles University Prague Czech Republic

University of Milano Bicocca MBBM Foundation ASST Monza Monza Italy

University of Tennessee Memphis TN

Citace poskytuje Crossref.org

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