Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

Abstract

Adult Philadelphia chromosome–positive (Ph+) or BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL) is an acute leukemia previously associated with a high relapse rate, short disease-free survival, and poor overall survival. In adults, allogeneic hematopoietic cell transplant in first remission remains the only proven curative strategy for transplant-eligible patients. The introduction of tyrosine kinase inhibitors (TKIS) in the treatment of patients with Ph+ or BCR-ABL+ ALL has significantly improved the depth and duration of complete remission, allowing more patients to proceed to transplantation. Although tkis are now considered a standard of care in this setting, few randomized trials have examined the optimal use of TKIS in patients with Ph+ ALL. Questions of major importance remain, including the best way to administer these medications, the choice of tki to administer, and the schedule and the duration to use. We present the results of a systematic review of the literature with consensus recommendations based on the available evidence.