Cario Gunnar, Valsecchi Maria Grazia, Conter Valentino, Gotti Giacomo, Möricke Anja, Stanulla Martin, Vossen-Gajcy Michaela, Lenk Lennart, Stary Jan, Hrusak Ondrej, Dworzak Michael, Attarbaschi Andishe, Barbaric Draga, Locatelli Franco, Bodmer Nicole, Elitzur Sarah, Silvestri Daniela, Dalla-Pozza Luciano, Fagioli Franca, Kulozik Andreas E, Izraeli Shai, Rizzari Carmelo, Rademacher Annika, Buldini Barbara, Bourquin Jean-Pierre, Zimmermann Martin, Schrappe Martin, Biondi Andrea
Department of Pediatrics I, Pediatric Hematology and Oncology, ALL-BFM Study Group University Medical Center Schleswig-Holstein, Campus Kiel Kiel Germany.
School of Medicine and Surgery University of Milan-Bicocca Monza Italy.
Hemasphere. 2025 Sep 2;9(9):e70206. doi: 10.1002/hem3.70206. eCollection 2025 Sep.
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 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 ( = 470); 71.9% ± 2.3% and 18.0% ± 1.9% in HR patients ( = 402). High PCR-MRD levels at EOI and EOC were prognostic in all models, with EOC-MRD ≥ 5 × 10 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 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 being candidate criteria for early stratification and intervention modifications.
为改善儿童T细胞急性淋巴细胞白血病（T-ALL）患者的治疗效果，AIEOP-BFM ALL 2009试验在AIEOP-BFM ALL 2000及其他儿童ALL研究组结果的基础上，对T-ALL分层及治疗方案进行了调整。本报告旨在描述AIEOP-BFM ALL 2009试验中T-ALL患者的治疗效果，并评估诱导治疗结束（EOI）时确定的预后特征，为未来方案的分层及干预提供依据。2010年6月至2017年2月，共纳入872例年龄在1至17岁的T-ALL患者。高危（HR）标准为泼尼松反应不佳（PPR）、第15天流式细胞术微小残留病（MRD）≥10%、EOI时未完全缓解或巩固治疗结束（EOC）时聚合酶链反应（PCR）-MRD≥5×10。通过三个无事件生存（EFS）的Cox回归模型评估预后因素。总体而言，5年EFS和生存率分别为79.9%±1.4%和84.9%±1.2%，累积复发率（CIR）和死亡率分别为13.0%±1.2%和5.9%±0.8%。非HR患者（n = 470）的5年EFS和CIR分别为86.8%±1.6%和8.7%±1.3%；HR患者（n = 402）的5年EFS和CIR分别为71.9%±2.3%和18.0%±1.9%。EOI和EOC时高PCR-MRD水平在所有模型中均具有预后意义，EOC-MRD≥5×10的风险比为6.22（P < 0.001）。当模型仅考虑EOI时确定的因素时，中枢神经系统（CNS）3（风险比 = 2.3，P < 0.001）、PPR（风险比 = 1.74，P = 0.02）和高EOI-MRD（≥5×10时风险比为4.71 vs. 阴性，P < 0.001）对EFS有显著影响。AIEOP-BFM ALL 2009试验中T-ALL患者的治疗效果良好。虽然EOC-MRD仍然是最强的预后预测指标，但PPR、CNS3疾病和EOI-MRD显示出相关的预后价值，CNS3和EOI-MRD≥5×10可作为早期分层及干预调整的候选标准。
