Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain.
Instituto de Investigación Biomédica de Salamanca (IBSAL), Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Universidad de Salamanca-Centro Superior de Investigaciones Científicas (CSIC), Hospital Universitario, Salamanca, Spain.
Blood. 2021 Apr 8;137(14):1879-1894. doi: 10.1182/blood.2020007311.
The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.
成人费城染色体阴性（Ph-）急性淋巴细胞白血病（ALL）伴高危（HR）特征和充分的可测量残留病（MRD）清除患者是否需要异基因造血干细胞移植（allo-HSCT）仍不清楚。ALL-HR-11 试验的目的是评估根据诱导和巩固期 MRD 水平接受化疗或 allo-HSCT 的 HR Ph-成人 ALL 患者的结局。年龄在 15 至 60 岁之间、具有 HR-ALL、完全缓解（CR）和 MRD 水平（通过 8 色流式细胞术中心评估）在诱导后<0.1%和在早期巩固后<0.01%的患者被分配接受延迟巩固和维持治疗，直至 CR 持续 2 年。其余患者被分配接受 allo-HSCT。348 例患者中有 315 例（91%）达到 CR，289 例患者中有 220 例（76%）在诱导后 MRD<0.1%。意向治疗分析中，218 例患者被分配接受化疗，106 例患者被分配接受 allo-HSCT。整个系列的 5 年（±95%置信区间）累积复发率（CIR）、总生存率（OS）和无事件生存率分别为 43%±7%、49%±7%和 40%±6%，化疗组的 CIR 和 OS 率分别为 45%±8%和 59%±9%，allo-HSCT 组分别为 40%±12%和 38%±11%。我们的结果表明，对于诱导和巩固后充分缓解的 60 岁以下高危 Ph-成人 ALL 患者，避免 allo-HSCT 不会影响其结局。对于 MRD 清除不良的患者，需要更好的缓解后替代治疗。该试验在 www.clinicaltrials.gov 上注册，编号为 NCT01540812。
