The Role of Allogeneic Hematopoietic Cell Transplantation in the Management of Philadelphia Chromosome‐Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors

Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL), the most common subtype of adult ALL, has undergone dramatic transformation in prognosis over the past two decades. Introduction of tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 fusion protein has revolutionized frontline therapy, with successive generations of TKIs-from imatinib to dasatinib and most recently ponatinib-achieving progressively deeper and more durable molecular responses. Concurrently, the integration of immunotherapy, particularly blinatumomab, has enabled chemotherapy-sparing approaches further improving tolerability and efficacy. These advances have fundamentally challenged the historical paradigm that allogeneic hematopoietic cell transplantation (HCT) is indispensable for all Ph+ ALL patients in first complete remission. The role of allogeneic HCT is often debated and increasingly individualized, guided by measurable residual disease (MRD) assessment, TKI generation, depth and duration of molecular response, and patient-specific factors. Emerging data suggest that a subset of patients achieving early, deep MRD negativity with TKIs and immunotherapy may achieve durable remissions without transplant, though long-term follow-up remains limited. For patients proceeding to allogeneic HCT, optimization of transplant strategy-including donor selection, conditioning intensity, graft-versus-host disease prophylaxis, and posttransplant TKI maintenance-is critical to maximize graft-versus-leukemia effects while minimizing toxicity. Treatment-free remission strategies following prolonged TKI maintenance in non-transplant patients, and the integration of chimeric antigen receptor (CAR) T-cell therapy as bridge, consolidation, or salvage, represent emerging frontiers. This review critically examines the contemporary role of allogeneic HCT in Ph+ ALL and provides a framework for transplant decision-making in the contemporary era of targeted and cellular immunotherapy.