The Role of Allogeneic Stem Cell Transplantation in Philadelphia Positive Acute Lymphoblastic Leukemia in the Era of Second- and Third-Generation TKI

Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) has historically been associated with a poor prognosis. The advent of tyrosine kinase inhibitors (TKIs) has significantly improved treatment outcomes, shifting the therapeutic landscape away from traditional chemotherapy-based approaches. Second-generation (dasatinib, nilotinib, bosutinib) and third-generation (ponatinib) TKIs have shown superior efficacy, deeper molecular responses, and improved survival rates. The role of allogeneic hematopoietic cell transplantation (allo-HCT) in the era of modern TKIs remains a subject of ongoing debate. Traditionally, allo-HCT was the only curative strategy; however, it was associated with transplant-related mortality (TRM) and graft-vs-host disease (GVHD), hence the survival benefit was controversial. Recent studies suggest that patients achieving deep molecular remission on TKI-based regimens may no longer require transplant. This chapter reviews the evolving role of allo-HCT in Ph + ALL, assessing its indications, timing, outcomes, and the integration of novel therapies such as monoclonal antibodies and chimeric antigen receptor T-cell (CAR-T) therapy. We discuss post-transplant TKI maintenance strategies, long-term complications, and emerging data on transplant-free approaches. A real-world clinical case is included to illustrate current decision-making in Ph + ALL.