Optimal approach to treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: how to best use all the available tools.

Approximately 20% of adult and 50% of elderly patients with acute lymphoblastic leukemia (ALL) express the t(9;22) chromosome translocation with BCR-ABL rearrangement. The use of tyrosine kinase inhibitors (TKIs) has resulted in higher rates of complete remission (95-100%), and many fit patients are able to receive allogeneic hematopoietic stem cell transplant (HSCT). TKI-containing induction followed by myeloablative allogeneic HSCT has resulted in long-term survival between 50 and 60% in young adults, and recent reports show promising results in patients submitted to non-myeloablative HSCT. The prognosis of elderly patients with Philadelphia chromosome-positive (Ph+) ALL is poor despite a high complete remission (CR) rate with TKIs and minimal chemotherapy, and improvements are clearly needed in this subgroup of patients. This review summarizes and discusses current challenges in the treatment of patients with Ph+ ALL, such as selection of the appropriate induction therapy, minimization of transplant toxicity, correct use of TKIs after transplant, BCR-ABL monitoring, the study of mutations which confer resistance to TKIs and new drugs to overcome this resistance.