The effect of cladribine-containing conditioning regimen on the efficacy and safety of allogeneic hematopoietic stem cell transplantation for children with acute lymphoblastic leukemia

Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for children with refractory, relapsed, or high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens are critical for ensuring engraftment and reducing post-transplantation relapse. Cladribine is a purine nucleoside analogue with antileukemic activity and central nervous system penetration. However, its role in conditioning regimens for pediatric ALL remains insufficiently defined. Methods We conducted a retrospective cohort study of 66 pediatric patients with ALL who underwent their first allo-HSCT at Sun Yat-sen Memorial Hospital between August 2018 and December 2023. Patients were stratified according to whether cladribine was incorporated into the conditioning regimen (CLAD + vs. CLAD-). Survival outcomes, relapse incidence, regimen-related toxicity, graft-versus-host disease (GVHD), and post-transplantation complications were compared. Sensitivity analyses were performed by restricting the control group to patients receiving non-total body irradiation, chemotherapy-based conditioning. Competing-risk methods were applied where appropriate. Results Among the 66 children who underwent allo-HSCT, 38 patients received CLAD+ conditioning and 28 received CLAD- regimens. Conditioning intensity scores were significantly lower in the CLAD+ group (4.0 [3.0, 5.0] vs. 4.5 [4.0, 4.5], p < 0.001). Two-year overall survival or transplantation-related mortality did not differ significantly between the two groups. However, the 2-year relapse-free survival was significantly higher in the CLAD+ group (94.44% vs. 81.16%, p = 0.019), with a significantly lower 2-year cumulative incidence of relapse. These findings remained directionally consistent in sensitivity analyses that accounted for regimen heterogeneity and competing risks. Hematopoietic engraftment, the incidence of acute and chronic GVHD, and major post-transplantation complications were comparable between the two groups, while renal and gastrointestinal toxicities were significantly less frequent in the CLAD+ group. Conclusion Incorporation cladribine into conditioning regimens for pediatric ALL is associated with improved relapse-free survival and significantly lower frequencies of renal and gastrointestinal toxicities, without increasing the risk of transplant-related complications. Given the retrospective design and limited number of events, these promising findings warrant prospective validation in future studies.