Ribera Josep-Maria, Morgades Mireia, Montesinos Pau, Tormo Mar, Martínez-Carballeira Daniel, González-Campos José, Gil Cristina, Barba Pere, García-Boyero Raimundo, Coll Rosa, Pedreño María, Ribera Jordi, Mercadal Santiago, Vives Susana, Novo Andrés, Genescà Eulàlia, Hernández-Rivas Jesús-María, Bergua Juan, Amigo María-Luz, Vall-Llovera Ferran, Martínez-Sánchez Pilar, Calbacho María, García-Cadenas Irene, Garcia-Guiñon Antoni, Sánchez-Sánchez María-José, Cervera Marta, Feliu Evarist, Orfao Alberto
Departments of Clinical Hematology, ICO-Hospital Germans Trias i Pujol. Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
Departments of Clinical Hematology, Hospital Universitari i Politècnic La Fe, CIBERONC, Instituto Carlos III, Valencia, Spain, Madrid, Spain.
Cancer Med. 2020 Apr;9(7):2317-2329. doi: 10.1002/cam4.2814. Epub 2020 Feb 5.
Pediatric-based or -inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL).
This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15-30 years with standard-risk (SR) ALL.
From 2008 to 2018, 89 patients (38 adolescents [15-18 years] and 51 young adults [YA, 19-30 years], median age: 20 [15-29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty-two patients were transferred to a high-risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high-level of end-induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%-47%), with significant differences between adolescents and YA: 13% (4%-28%) vs 52% (34%-67%), P = .012. No treatment-related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5-year overall survival (OS) was 74% (95%CI: 63%-85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%-100%) vs 63% (46%-80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%-47%] vs 37% [14%-61%]; OS: 78% [66%-90%] vs 61% [31%;91%]).
A full pediatric trial is feasible and effective for AYA with Ph-neg, SR-ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior.
以儿童为基础或受儿童启发的试验改善了费城染色体阴性（Ph-neg）急性淋巴细胞白血病（ALL）的青少年和青年（AYA）患者的预后。
本研究报告了ALLRE08试验的治疗结果，这是一项针对15至30岁标准风险（SR）ALL的AYA患者的完整儿童试验。
2008年至2018年，89例患者（38例青少年[15 - 18岁]和51例青年[YA，19 - 30岁]，中位年龄：20[15 - 29]岁）纳入ALLRE08试验。完全缓解（CR）率为95%。22例患者因第14天骨髓反应不佳（n = 20）或诱导末期微小残留反应水平高（MRD≥0.25%，n = 2）而转入高风险（HR）方案。5年复发累积发生率（CIR）为35%（95%CI：23% - 47%），青少年和青年之间存在显著差异：13%（4% - 28%）对52%（34% - 67%），P = 0.012。ALLRE08试验后的66/66例患者与转入HR试验的23/23例患者中均未观察到治疗相关死亡。估计5年总生存率（OS）为74%（95%CI：63% - 85%），青少年的生存率显著高于青年：87%（95%CI：74% - 100%）对63%（46% - 80%），P = 0.021。尽管转入HR试验的患者的CIR或OS较低，但差异无统计学意义（CIR：34%[21% - 47%]对37%[14% - 61%]；OS：78%[66% - 90%]对61%[31%；91%]）。
对于Ph-neg、SR-ALL的AYA患者，完整的儿童试验是可行且有效的，青少年的结果优于青年。通过HR试验挽救的早期反应不佳患者的结局并无显著劣势。
