Current Approach to Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Abstract

Introduction Prior to the advent of tyrosine kinase inhibitors (TKI), expected overall survival (OS) for patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was estimated at best ~20%, and thus consolidation with allogeneic hematopoietic cell transplantation (HCT) was uniformly recommended. The international ALL trial MRC UKALLXII/ECOG2993 showed that allogeneic HCT was superior to chemotherapy in 267 adults with Ph+ ALL (5-year OS was 44% after matched sibling allogeneic HCT, 36% after MUD HCT, and 19% after chemotherapy only).1 However, the introduction of BCR-ABL1 targeted therapy with highly potent TKIs has significantly improved outcomes for this subset of ALL patients, resulting in greater numbers of remissions, and more transplant-eligible patients.2–4 Furthermore, some retrospective analyses suggest that transplant may not be needed in patients who go into a deep remission, without detectable measurable residual disease (MRD), following TKI therapy. Herein, we will review data from recent studies that are used to inform our recommendations regarding therapy in the contemporary era for newly diagnosed patients with Ph+ ALL.