Refining Risk Stratification for B-cell Precursor Adult Acute Lymphoblastic Leukemia Treated With a Pediatric-inspired Regimen by Combining IKZF1 Deletion and Minimal Residual Disease.

Minimal residual disease (MRD) is the most important prognostic factor for B-cell acute lymphoblastic leukemia (B-ALL) however nearly 20% to 30% of patients relapsed even when they achieved negative MRD, how to identify these patients is less addressed. In this study, we aimed to reassess the prognostic significance of MRD and IKZF1 in adult B-ALL patients receiving pediatric chemotherapy regimens. In the PDT-ALL-2016 cohort (NCT03564470), adult B-ALL patients were treated with a pediatric-inspired regimen; patients were redefined as standard (MRD-negative and IKZF1wild-type), intermediate (MRD-positive or IKZF1 deletion), and high-risk (MRD-positive and IKZF1 deletion) groups by combining IKZF1 deletion status and MRD. Furthermore, the prognostic panel of IKZF1 deletion and/or MRD-positive was confirmed in the independent cohort from the COG-P9906 dataset. In the high- and intermediate-risk groups, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was strongly associated with higher 5-year overall survival (OS), higher leukemia-free survival (LFS), and lower cumulative incidence of relapse (CIR). In the standard-risk group, there was no significant advantage in the 5-year OS, LFS, and CIR of patients who received allo-HSCT versus those who received chemotherapy. Our study demonstrated that combining early MRD response and IKZF1 deletion allows for better risk stratification of patients to identify those who may benefit from allo-HSCT in the context of an intensified pediatric-inspired regimen.