Predictors of complete molecular response and impact of allogeneic hematopoietic stem cell transplantation on outcome in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL): results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)

With the advent of tyrosine kinase inhibitors (TKIs), the outcomes of patients with Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) improved. We conducted a retrospective multicenter study of 467 adult patients with Ph + ALL (2003-2023) evaluating predictors of complete molecular response (CMR) at 3 months and its impact on outcomes. CMR was achieved in 297(63.7%) patients. In the multivariate analysis, WBC > 70,000/L at diagnosis (p = 0.01), p210 BCR::ABL1 fusion (p < 0.001) and monosomy 7 (p = 0.007) were independently associated with failure to achieve CMR, while use of ponatinib or dasatinib (p = 0.008) and intensive chemotherapy (IC) (p = 0.009) predicted higher CMR. Among patients who achieved CMR, the median relapse-free survival (RFS) was significantly better (123.1 vs. 30.3 months, p < 0.0001), however, overall survival (OS) was not significantly different (129.2. vs. 149.3 months, p = 0.07) with or without allogeneic hematopoietic cell transplantation (allo-HCT). These findings suggest that allo-HCT may be deferred in selected patients achieving early CMR, although prospective validation is needed.