A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: Results of the ALLRE08 PETHEMA trial

Ribera JM; Morgades M; Montesinos P; Tormo M; Martínez-Carballeira D; González-Campos J; Gil C; Barba P; García-Boyero R; Coll R; Pedreño M; Ribera J; Mercadal S; Vives S; Novo A; Genescà E; Hernández-Rivas JM; Bergua J; Amigo ML; Vall-Llovera F; Martínez-Sánchez P; Calbacho M; García-Cadenas I; Garcia-Guiñon A; Sánchez-Sánchez MJ; Cervera M; Feliu E; Orfao A. PETHEMA Group; Spanish Society of Hematology.


Background 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). Methods 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. Results 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%]). Conclusion 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.

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