Acute Lymphoid Leukemia: Is Transplant Indicated for Philadelphia Chromosome Positive ALL?

Abstract

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a distinct subtype of ALL that has historically been associated with a very poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloHSCT) has improved the 5-year overall survival rate to approximately 44% and has been considered the only potentially curative treatment option for these patients. The introduction of tyrosine kinase inhibitors (TKIs) represented a breakthrough in the management of Ph+ ALL, significantly improving patient outcomes. Imatinib, the first-generation TKI, led to high complete remission (CR) rates when added to induction and consolidation chemotherapy. Next-generation TKIs, such as dasatinib and ponatinib, have also demonstrated remarkably high CR rates, even when combined with reduced-intensity chemotherapy or steroids. The advent of immunotherapies, including inotuzumab ozogamicin, blinatumomab, and chimeric antigen receptor T-cell (CAR-T) therapy, was another major milestone in Ph+ ALL treatment. The combination of TKIs with immunotherapy appears to be an optimal therapeutic strategy. Given the efficacy of these chemotherapy-free approaches, the role of alloHSCT in Ph+ ALL needs to be reassessed. Patients treated with next-generation TKIs, particularly in combination with novel immunotherapies, may achieve durable remissions without the need for alloHSCT, provided they do not harbour additional adverse cytogenetic or molecular abnormalities and achieve a deep response following induction and consolidation therapy.

Keywords: Allogeneic hematopoietic stem cell transplantation (alloHSCT); Blinatumomab; Chemotherapy-free treatment; Chimeric antigen receptor T cell therapy (CAR-T); Immunotherapy; Inotuzumab ozogamicin; Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); Tyrosine kinase inhibitor (TKI).