Treatments for Philadelphia chromosome-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era

Abstract

The introduction of imatinib (IM) has led to a paradigm shift in the treatment strategy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). After introducing IM, second- and third-generation tyrosine kinase inhibitors (TKIs), which have stronger BCR-ABL1 inhibitory activity than IM, have appeared and their therapeutic results are beginning to be reported. However, to date, no comparison study between individual TKI and the current treatment strategy for Ph + ALL has been performed considering either a TKI-based regimen in induction followed by combination chemotherapy with a TKI or allogeneic hematopoietic stem cell transplantation (alloSCT). In the case of treating with ponatinib, it was suggested that the inclusion of alloSCT into the treatment strategy could be avoided. Because alloSCT has an appreciable treatment-related mortality rate and an upper age limit, the treatment strategy without alloSCT may remain mainstream in the future. Chemotherapy-free treatments, such as a TKI plus a monoclonal antibody or immunotherapy, are also expected to gain traction an alternate strategy and are now under investigation.