The role of tyrosine kinase inhibitors as a post-hematopoietic stem cell transplant maintenance therapy for pediatric acute leukemia.

Abstract

e22003 Background: Hematopoietic stem cell transplantation (HSCT) is a critical component of care for pediatric acute leukemia patients. Relapse following HSCT is a leading cause of transplant failure, emphasizing the need for effective post-transplant maintenance therapy. Tyrosine kinase inhibitors (TKIs) block the signaling pathways essential for leukemic cell growth and proliferation, and they are clinically useful for treating a wide variety of cancers. This systematic review aims to evaluate the role of tyrosine kinase inhibitors as a post-HSCT maintenance therapy in pediatric acute leukemia. Methods: The authors conducted a literature search of the PubMed, Cochrane, Web of Science, and VHL libraries according to PRISMA guidelines. All original studies were included if they were relevant to the research question and fit the eligibility criteria. Quality assessment for observational studies was done using STROBE and for case reports was done using CARE. Risk of bias for observational studies was assessed using ROBINS-I. Results: The initial search identified 765 articles, and after filtration, the final number included was 16. TKIs were used in patients with chromosomal alterations that result in fusion proteins with constitutively active tyrosine kinase activity in order to prevent relapse, particularly in high-risk patients with positive minimal residual disease (MRD). The specific TKI was chosen based on disease status and molecular profiling. Imatinib, dasatinib, and ponatinib were frequently used for Philadelphia-chromosome-positive acute lymphoblastic leukemia to target the BCR-ABL fusion kinase. Sorafenib was often used for FLT3-ITD-positive acute myeloid leukemia to target the FLT3 kinase. The duration of maintenance ranged from 10 months to 3 years, with dosage dependent on the specific drug and tolerability. Reported side effects included cytopenia, liver dysfunction, and skin conditions, but TKIs were found to be generally well-tolerated in this population. Overall, TKIs were an effective and well-tolerated maintenance therapy for preventing relapse in pediatric patients post-HSCT, with many patients achieving MRD negativity and sustaining complete remission. However, duration and safety need to be further studied in the pediatric population to develop standardized treatment regimens. Conclusions: TKIs can serve as targeted post-HSCT maintenance therapy in select pediatric acute leukemia patients, particularly those with high-risk, mutation-driven disease. Molecular profiling and MRD monitoring are central to clinical decision-making, guiding agent selection, timing, and mutation-directed therapy adjustments. These findings support the individualized use of TKIs to reduce relapse risk following HSCT, while highlighting the need for prospective studies to define standardized treatment strategies.