Current management of Philadelphia chromosome positive ALL and the role of stem cell transplantation

Abstract

Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population. Long-term data using chemotherapy and TKI combinations demonstrate that a proportion of patients treated can achieve durable relapse-free survival without undergoing alloHCT. Furthermore, the availability of sensitive minimal residual disease monitoring assays may allow early detection of the patients who are more likely to relapse and who are likely candidates for early alloHCT. The emergence of more potent TKIs with significant activity against resistant mutations has allowed deintensification of chemotherapy regimens. Available data indicate that complete reliance on TKIs, alone or with minimal additional therapy, and elimination of more intensive chemotherapy or alloHCT is unlikely to achieve long term cure in most patients. However, introduction of other highly effective agents that can be combined with TKIs may allow further minimization of chemotherapy and alloHCT in the future, as we have witnessed in acute promyelocytic leukemia.

Conflict of interest statement

Conflict-of-interest disclosure: The author has received research funding from Amgen, Bristol Myers Squibb, and Seattle Genetics; has consulted for Ariad, Amgen, and Seattle Genetics; and has received honoraria from Ariad, Amgen, and Seattle Genetics.

© 2016 by The American Society of Hematology. All rights reserved.