To improve the outcome of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients, the AIEOP-BFM ALL 2009 trial modified T-ALL stratification and treatment based on AIEOP-BFM ALL 2000 and other pediatric ALL groups' results. This report aims to describe the outcome of T-ALL patients in trial AIEOP-BFM ALL 2009 and evaluate prognostic features defined within the end of induction (EOI) therapy, for future protocols stratification and interventions. From 06/2010 to 02/2017, 872 T-ALL patients, aged 1-17, were enrolled. High risk (HR) criteria were prednisone poor response (PPR), Day 15 flow cytometry minimal residual disease (MRD) ≥ 10%, no complete remission at EOI, or polymerase chain reaction (PCR)-MRD ≥ 5 × 10-4 at end of consolidation (EOC). Three Cox regression models on event-free survival (EFS) evaluated prognostic factors. Overall, 5-year EFS and survival were 79.9% ± 1.4% and 84.9% ± 1.2% with cumulative incidence of relapse (CIR) and death of 13.0% ± 1.2% and 5.9% ± 0.8%. Five-year EFS and CIR were 86.8% ± 1.6% and 8.7% ± 1.3% in non-HR patients (n = 470); 71.9% ± 2.3% and 18.0% ± 1.9% in HR patients (n = 402). High PCR-MRD levels at EOI and EOC were prognostic in all models, with EOC-MRD ≥ 5 × 10-3 related to a hazard ratio of 6.22 (P < 0.001). When a model considered factors identified at EOI only, central nervous system (CNS)3 (hazard ratio = 2.3, P < 0.001), PPR (hazard ratio = 1.74, P = 0.02), and high EOI-MRD (hazard ratio 4.71 for ≥5 × 10-2 vs. negative, P < 0.001) significantly impacted EFS. Results of T-ALL patients in AIEOP-BFM ALL 2009 were favorable. While EOC-MRD remained the strongest prognostic predictor, PPR, CNS3 disease, and EOI-MRD showed relevant prognostic value, with CNS3 and EOI-MRD ≥ 5 × 10-2 being candidate criteria for early stratification and intervention modifications.

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

Cancer Center for Children The Children's Hospital Westmead Sydney New South Wales Australia

Catholic University of the Sacred Heart Rome Italy

Department of Hematology Oncology and Cell and Gene Therapy IRCCS Bambino Gesù Children's Hospital Rome Italy

Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology Clinic and Lab University of Padova Padua Italy

Department of Pediatric Hematology and Oncology Hannover Medical School Hannover Germany

Department of Pediatric Hematology and Oncology Schneider Children's Medical Center and Faculty of Medicine Tel Aviv University Tel Aviv Israel

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

Department of Pediatric Oncology Hematology and Immunology Heidelberg University Heidelberg Germany

Department of Pediatric Oncology University Children's Hospital Zürich Zürich Switzerland

Department of Pediatrics 1 Pediatric Hematology and Oncology ALL BFM Study Group University Medical Center Schleswig Holstein Campus Kiel Kiel Germany

Department of Pediatrics and Adolescent Medicine St Anna Children's Hospital Medical University of Vienna Vienna Austria

Department of Women's and Children's Health Padua Italy

Kids Cancer Centre Sydney Children's Hospital Randwick New South Wales Australia

Pediatric Oncology Department Regina Margherita Children's Hospital Città della Salute e della Scienza University Hospital Torino Italy

Pediatrics Fondazione IRCCS San Gerardo dei Tintori Monza Italy

School of Clinical Medicine UNSW Sydney Sydney New South Wales Australia

School of Medicine and Surgery University of Milan Bicocca Monza Italy

St Anna Children's Cancer Research Institute Vienna Austria

Tettamanti Center Fondazione IRCCS San Gerardo dei Tintori Monza Italy

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