The Role of Transplant for Philadelphia-positive B-cell Acute Lymphoblastic Leukemia in 2025

Abstract

Purpose of review: This review expands upon the evolving role of allo-HSCT, integrating current clinical evidence, emerging therapies, and novel risk-adapted strategies for managing adult with Ph + ALL in the contemporary era.

Recent findings: Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL) is the most common genetically defined subtype of B-cell ALL. The treatment of Ph + ALL has witnessed significant advancements over the past two decades following the introduction of BCR::ABL1 tyrosine kinase inhibitors (TKIs). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has long been a cornerstone treatment in adult patients with Ph + ALL, offering the most reliable disease curative potential, and the early use of TKIs has led to successfully transplanting more patients. Lately, the early introduction of more potent TKIs and blinatumomab have further reshaped the frontline treatment paradigm of Ph + ALL and resulted into improved outcomes even in the absence of transplant consolidation. Simultaneously, our ability to stratify disease risk has greatly enhanced with the advent of ultrasensitive measurable residual disease (MRD) assessment tools and the utilization of comprehensive disease molecular profiling, and thus, identifying lower risk patients who can be cured with non-transplant approaches. With evolving treatment options for Ph + ALL, the historical notion that allo-HSCT in first complete remission is essential to cure all adult patients with Ph + ALL is being challenged and the benefit of consolidation with transplant may extend to certain patient populations.

Keywords: Allogeneic stem cell transplantation; B-cell ALL; Philadelphia-positive B-cell ALL.