SOHO State of the Art Update and Next Questions: Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

The widespread adoption of Bcr-Abl-directed tyrosine kinase inhibitors (TKIs) into first-line regimens for patients with Philadelphia chromosome (Ph)-positive (Ph⁺) acute lymphoblastic leukemia (ALL) has revolutionized the outcomes of patients with this disease. Whereas Ph⁺ ALL was historically associated with cure rates of <25% in the pre-TKI era, now long-term survival in more than 75% of patients has been reported. With the promising efficacy of later-generation TKIs (eg, ponatinib) and the emerging understanding of the prognostic significance of various cooperative genomic alterations and of minimal residual disease, the widespread use of allogeneic hematopoietic stem cell transplantation in first remission for patients with Ph⁺ ALL has been increasingly questioned. Furthermore, with the development of more potent Bcr-Abl TKIs, several studies are evaluating novel strategies that reduce or eliminate chemotherapy. Herein, we review the major genomic and molecular prognostic factors in Ph⁺ ALL and also discuss the current and future treatment paradigms for this disease.