PURPOSE: Historically, patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission at the end of induction (EOI) have had poor long-term survival. The goal of this study was to examine the efficacy of contemporary therapy, including allogeneic hematopoietic stem cell transplantation (HSCT) in first remission (CR1). METHODS: Induction failure (IF) was defined as the persistence of at least 5% bone marrow (BM) lymphoblasts and/or extramedullary disease after 4-6 weeks of induction chemotherapy. Disease features and clinical outcomes were reported in 325 of 6,167 (5%) patients age 21 years and younger treated in 14 cooperative study groups between 2000 and 2018. RESULTS: With a median follow-up period of 6.4 years (range, 0.3-17.9 years), the 10-year overall survival (OS) was 54.7% (SE = 2.9), which is significantly higher than the 27.6% (SE = 2.9) observed in the historical cohort from 1985 to 2000. There was no significant impact of sex, age, white blood cell count, central nervous system disease status, T-cell maturity, or BM disease burden at EOI on OS. Postinduction complete remission (CR) was achieved in 93% of patients with 10-year OS of 59.6% (SE = 3.1%) and disease-free survival (DFS) of 56.3% (SE = 3.1%). Among the patients who achieved CR, 72% underwent HSCT and their 10-year DFS (with a 190-day landmark) was significantly better than nontransplanted patients (63.8% [SE = 3.6] v 45.5% [SE = 7.1]; P = .005), with OS of 66.2% (SE = 3.6) versus 50.8% (SE = 6.8); P = .10, respectively. CONCLUSION: Outcomes for patients age 21 years and younger with T-ALL and IF have improved in the contemporary treatment era with a DFS benefit among those undergoing HSCT in CR1. However, outcomes still lag considerably behind those who achieve remission at EOI, warranting investigation of new treatment approaches.

Bicocca Bioinformatics Biostatistics and Bioimaging Center B4 School of Medicine and Surgery University of Milano Bicocca Milan Italy

Biostatistics and Clinical Epidemiology Fondazione IRCCS San Gerardo dei Tintori Monza Italy

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 Haematology Great Ormond Street Hospital London United Kingdom

Department of Oncology St Jude Children's Research Hospital Memphis TN

Department of Paediatrics Yong Loo Lin School of Medicine National University of Singapore Singapore

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology St Anna Children's Hospital Medical University of Vienna Vienna Austria

Department of Pediatric Hematology Oncology and Stem Cell Transplantation Ghent University Hospital Ghent Belgium

Department of Pediatric Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA

Department of Pediatrics and Adolescent Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Pediatrics and Perlmutter Cancer Center NYU Langone Health New York NY

Department of Pediatrics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

Department of Woman and Child Health University of Padua Padua Italy

Institute of Clinical Medicine Faculty of Medicine University of Copenhagen Denmark

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

Pediatric Hematology and Oncology Kinderspital Zurich Zurich Switzerland

Pediatrics 1 University Medical Center Schleswig Holstein Campus Kiel Kiel Germany

Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

Schneider Children's Medical Center and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

St Anna Children's Cancer Research Institute Vienna Austria

Tettamanti Center Fondazione IRCCS San Gerardo dei Tintori Monza Italy

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