Dynamics of minimal residual disease defines a novel risk-classification and the role of allo-HSCT in adult Ph-negative B-cell acute lymphoblastic leukemia

Abstract

The prognosis of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients is well established. However, the implementation of dynamic MRD for risk classification and decision-making for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains vague. In this study, we collected multiparameter flow cytometry (MFC)-MRD data of Ph-negative B-ALL patients (n = 134) from the Precision-Classification-Directed-Target-Total-Therapy-ALL-2016 (PDT-ALL-2016) cohort and stratified it into high-(HR), medium-(MR), and standard-risk (SR) groups. With a median of 3.65 years follow-up (95% CI: 3.037–4.263), 3-year OS rate was 51.8 ± 8.3% in HR, compared with MR 61.5 ± 10.8% (p = 0.472), and SR 73.3 ± 5.9% (p = 0.006). Multivariate analysis shows that integrated dynamic MRD is an independent factor for overall survival. Compared to pediatric-inspired chemotherapy, allo-HSCT significantly improves the survival of the HR cohort (p < 0.001), but not in MR and SR. Finally, our study suggests that integrated dynamic MRD defines a novel risk-classification criteria and highlights the benefits of allo-HSCT in adult patients with Ph-negative ALL.