Management of Philadelphia chromosome positive acute lymphoblastic leukemia in the current era

Before the advent of tyrosine kinase inhibitors (TKI) the outcome of Philadelphia chromosome positive (Ph⁺) acute lymphoblastic leukemia (ALL) was dismal. The TKI combination with induction regimens has greatly improved the long-term outcome of Ph⁺ ALL, specifically ponatinib a most potent TKI in combination with HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) chemotherapy has demonstrated 5 years overall survival up to 75%. Historically, allogeneic hematopoietic stem cell transplantation (allo-HSCT) used to be the only potential curative option, recent data suggest that patients who achieve complete molecular remission within 3 months of TKI based induction therapies can achieve comparable overall survival with or without allo-HSCT. Intensive cytotoxic chemotherapy may not be the desirable treatment option in elderly Ph⁺ ALL patients due to anticipated tolerance, recently in a phase II study, “chemotherapy free” combinations such as blinatumomab (bispecific anti-CD3 and anti-CD19 monoclonal antibody) with ponatinib in treatment naïve Ph⁺ ALL patients have shown a complete response rate of 95% and 2 years overall survival of 93%. In this review we have highlighted the evolving treatment landscape of Ph⁺ ALL and what to look for in future.