Imatinib combined chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: Major challenges in current practice

The prognosis of Philadelphia chromosome-positive (Ph+) and/or BCR-ABL-positive acute lymphoblastic leukemia ( ALL) is extremely poor, and for decades allogeneic hematopoietic stem cell transplantation (HSCT) has been considered the only option for a cure. However, the treatment for Ph+ALL has been rapidly changing since imatinib, a selective inhibitor of the ABL tyrosine kinase, was introduced. Earlier clinical trials in which a moderate anti-leukemic effect of imatinib monotherapy was demonstrated have prompted investigators to explore the combination of imatinib and chemotherapy. The results of multiple studies indicate that chemotherapy combined with imatinib is well tolerated, induces complete hematological remission in almost every patient with newly diagnosed Ph+ALL, and molecular remission in more than half of the cases. Future clinical studies need to focus on how imatinib can be incorporated into chemotherapy more effectively by determining the optimal dosage of imatinib, the optimal combinational schedule, and the role of allogeneic HSCT.