Chemotherapy regimens with second generation tyrosine kinase inhibitors for BCR-ABL B-cell acute lymphoblastic leukemia: comparative outcomes and role of allogeneic hematopoietic cell transplantation.

Outcomes for adults with Philadelphia chromosome positive pre-B cell acute lymphoblastic leukemia (Ph + B-ALL) have improved dramatically, but questions remain regarding the optimal induction regimen and role of allogeneic hematopoietic cell transplantation (alloHCT). We analyzed 60 consecutive patients who received reduced-intensity (RII) or hyper-CVAD induction with continuous, second-generation tyrosine kinase inhibitors (TKIs). Reduced hematologic toxicity occurred after RII. Measurable residual disease (MRD) clearance by multicolor flow cytometry (MFC, 61 vs. 94%, p = 0.02) favored hyper-CVAD, but subsequent MRD-directed blinatumomab negated this difference. Four-year relapse-free survival (RFS) was 72.3% (95% confidence interval: 57.4-91.0%) and 79.8% (65.4-97.3%, p = 0.3) in RII and hyper-CVAD groups, respectively. AlloHCT, predominantly using reduced-intensity conditioning, bone marrow grafts, and post-transplant cyclophosphamide, was the only variable associated with improved overall survival on multivariate analysis. Concurrent chemotherapy and TKIs followed by blinatumomab for MRD positivity and alloHCT, all in less intensive forms, yield excellent outcomes for patients with Ph + B-ALL.