Role of Allogeneic Hematopoietic Stem-Cell Transplant Following TKI-Blinatumomab Induction for Ph-Positive Acute Lymphoblastic Leukemia in Adults

Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) has traditionally been treated with tyrosine kinase inhibitors (TKIs) and systemic chemotherapy, often followed by allogeneic hematopoietic stem cell transplant (HCT). More recently, chemotherapy-free induction regimens combining TKIs and blinatumomab have demonstrated efficacy with reduced risk for chemotherapy-related toxicity. However, the benefit of allogeneic HCT in this setting remains unclear. Objective: Compare relapse-free survival (RFS), overall survival (OS), and infection rates in adult patients with Ph-positive ALL treated with TKI and blinatumomab induction, stratified by allogeneic HCT status, using retrospective data. Study Design: We conducted a retrospective cohort study using the TriNetX global federated electronic health record database. Adult patients with Ph-positive ALL treated with TKI (dasatinib or ponatinib) and blinatumomab were stratified by receipt of allogeneic HCT (HCT+ vs HCT-). Propensity score matching (PSM) was applied to control for baseline demographics, comorbidities, medications, and laboratory values. Outcomes included RFS, OS, and infection rates. Results: A total of 242 patients were included, with 162 in the HCT- cohort and 80 in the HCT+ cohort. Following PSM, 56 patients remain in each cohort. There were no significant differences in RFS (HR 0.795; 95% CI: 0.283-2.239; p = 0.664) or OS (HR 0.734; 95% CI: 0.240-2.248; p = 0.587) between groups following PSM. However, HCT was associated with a significantly higher risk of infections, including bacterial, viral, and COVID-19 infections (all p < 0.01). These findings remained consistent after PSM. Conclusions: Among adults with Ph-positive ALL treated with TKI and blinatumomab, allogeneic HCT was not associated with improved RFS or OS but was linked to increased infection risk. These findings support a more selective approach to transplant following chemotherapy-free induction, particularly in patients with high baseline infection risk. Prospective studies incorporating measurable residual disease (MRD) status are warranted to further guide transplant decisions in this evolving therapeutic landscape.