Prophylactic or preemptive tyrosine kinase inhibitor therapy after allogeneic hematopoietic cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Abstract

Prevention of disease relapse after allogeneic hematopoietic cell transplantation (allo-HCT) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia remains a major concern. Maintenance therapy with tyrosine kinase inhibitors (TKIs) after allo-HCT has been used to reduce the incidence of relapse. Two main strategies are employed for using TKIs after allo-HCT: prophylactic TKI therapy, which is given before measurable residual disease (MRD) detection, and preemptive TKI therapy, which is given after MRD detection. These strategies both have advantages and disadvantages in terms of treatment efficacy, adverse events, adherence, and socioeconomic factors. In addition, many issues remain to be resolved because of the lack of large prospective studies on how to use TKIs after allo-HCT. These include indications for prophylactic and preemptive TKI therapy, timing of initiation, frequency of MRD monitoring, TKI selection, dose, and treatment duration. While the current available evidence is extremely limited, this article will discuss these issues after summarizing some representative and recent studies. It will also share a novel indicator that can be used to visualize the reversible transition between molecular relapse and remission by TKI therapy.