How I treat adult Ph-positive ALL

The Philadelphia (Ph) chromosome is one of the few genetic aberrations in which a casualty has been proven, and as such represents a success in the history of medicine. This is also evident in the setting of Ph+ acute lymphoblastic leukemia (Ph+ ALL), the most frequent genetic subgroup in adult ALL, whose incidence increases with age and whose prognosis, prior to the advent of tyrosine kinase inhibitors (TKIs), was particularly poor. The outcome and management of Ph+ ALL patients have greatly improved since the incorporation of 1st, 2nd and 3rd generations TKIs in the therapeutic backbone, and is further changing with the more recent introduction of immunotherapy. This is allowing long-term survival rates currently ranging between 75 and 80%. The clinical scenario of adult Ph+ ALL has thus changed profoundly, and new challenges are emerging. In this How I treat, illustrative clinical cases are used to discuss the role today of systemic chemotherapy and allogeneic stem cell transplant, the difficulty in treating central nervous system relapses and, more in general, relapses in the current therapeutic era, and the possibility of stopping TKIs. Finally, the challenges related to an optimal management of these patients is discussed.