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 naive 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. (c) 2023 Elsevier Masson SAS. All rights reserved.