PASS‐ALL study of paediatric‐inspired versus adult chemotherapy regimens on survival of high‐risk Philadelphia‐negative B‐cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation

Abstract

SummaryThis PASS‐ALL study was designed to explore the effect of paediatric‐inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high‐risk Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukaemia (HR PH‐ve B‐cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo‐HSCT). The PASS‐ALL study is a multicentre, observational cohort study, and 143 patients with HR B‐cell PH‐ve ALL were enrolled from five centres—77 patients allocated in the paediatric‐inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo‐HSCT. Three‐year leukaemia‐free survival (LFS) in the paediatric‐inspired cohort was 72.2% (95% CI 60.8%–83.6%) compared with 44.6% (95% CI 31.9%–57.3%; p = 0.001). Furthermore, time‐to‐positive minimal residual disease (TTP‐MRD) post‐HSCT was marked different, 3‐year cumulative incidence of relapse was 25.9% (95% CI 15.8%–37.2%) in paediatric cohort and 45.4% (95% CI 40.0%–57.9%) in adult cohort (p = 0.026). Finally, the 3‐year OS rate was 75.3% (95% CI 64.9%–85.7%) for the paediatric‐inspired cohort and 64.1% (95% CI 51.8%–76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric‐inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327–4.862, p = 0.005). Collectively, our data suggest that paediatric‐inspired chemotherapy pre‐HSCT results in deeper and durable MRD response reduces relapse post‐HSCT and improves survival in HR B‐cell PH‐ve ALL patients with allo‐HSCT.