BRIDGING THE GAP IN POST-TRANSPLANT CARE FOR PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (ALL): INNOVATIVE MAINTENANCE STRATEGIES TO REDUCE RELAPSE RATE AND ENHANCE SURVIVAL

Abstract

Relapsed Acute Lymphoblastic Leukemia (ALL) post-hematopoietic stem cell transplantation (HCT) have very poor outcomes. Patients face increased toxicity and poorer responses to therapy. With limited access to Chimeric Antigen Receptor (CAR) T-cell therapy, and the toxicity of a second HCT, alternative strategies are critically needed. Objective: To evaluate the impact of novel maintenance therapies post-HCT in pediatric ALL on reduce relapse rates and survival outcomes. Methods: This is a retrospective study of 64 pediatric ALL patients who underwent HCT between 2014 and 2024. From 2021 on, T-cell ALL, and B-cell ALL transplanted with measurable disease, primary refractory disease, or post-second HCT and who had adequate clinical conditions and access, received maintenance therapy. The maintenance therapies included tyrosine kinase inhibitors, blinatumomab, inotuzumab, hypomethylating agents and venetoclax. Data on demographics, treatment regimens, and clinical outcomes were retrospectively collected. Results: Maintenance was administered to 38% of patients. All but three were transplanted after 2020. The median start of maintenance was on D+52 and the duration 6 months. Of the 10 patients with T-ALL, 6 underwent maintenance therapy with only 1 relapse (16%), while 2 out of 4 (50%) who did not receive the prophylaxis relapsed. Of the 54 patients with B-ALL, 18 received maintenance and 5 relapsed (27%) after a median time of 273 days (137-535 days). Considering 10 patients who received blinatumomab, 2 relapsed (20%). Of the 36 patients who did not receive maintenance, 31% relapsed with a median time of 105 days (63-615 days). No patient had poor graft function or graft failure after maintenance. There was no mortality from infectious causes in this group. The overall survival, disease-free survival, and follow-up time for who did not receive maintenance therapy were 46%, 45%, and 56 months, and for who did, were 74%, 67%, and 22 months, respectively. Conclusion: Maintenance therapy delayed relapse (median of 273 vs 105 days) and improved overall survival. Blinatumomab maintenance was notably effective, reducing the relapse rate to 20%. Similarly, patients with T-ALL who underwent venetoclax-based maintenance therapy also experienced significantly lower relapse rates (16% vs 50%). Our findings suggest a substantial benefit of maintenance therapy in enhancing DFS and OS in pediatric ALL post-HCT. These promising results support further research to refine maintenance strategi es and validate findings in a larger cohort.