Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Adults

SIMPLE SUMMARY: Outcome of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) dramatically improved during the past 20 years with the advent of tyrosine kinase inhibitors and monoclonal antibodies. Their great efficacy in young and fit patients led to question our reliance on chemotherapy and allogeneic hematopoietic stem cell transplantation. Moreover, these well-tolerated treatments can be safely administrated even in the elderly that represent the majority of Ph+ ALL patient. This review will focus on the recent changes of paradigm in the management of Ph+ ALL patients and the development of novel therapeutic strategies. ABSTRACT: Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is the most common subtype of B-ALL in adults and its incidence increases with age. It is characterized by the presence of BCR-ABL oncoprotein that plays a central role in the leukemogenesis of Ph+ ALL. Ph+ ALL patients traditionally had dismal prognosis and long-term survivors were only observed among patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). However, feasibility of allo-HSCT is limited in this elderly population. Fortunately, development of increasingly powerful tyrosine kinase inhibitors (TKIs) from the beginning of the 2000′s dramatically improved the prognosis of Ph+ ALL patients with complete response rates above 90%, deep molecular responses and prolonged survival, altogether with good tolerance. TKIs became the keystone of Ph+ ALL management and their great efficacy led to develop reduced-intensity chemotherapy backbones. Subsequent introduction of blinatumomab allowed going further with development of chemo free strategies. This review will focus on these amazing recent advances as well as novel therapeutic strategies in adult Ph+ ALL.