Efficacy and safety of a new cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with relapsed or refractory acute myeloid leukemia

Abstract

Objectives: Cladribine, a synthetic analog of deoxyadenosine, exhibits potent activity against hematological malignancies. While cladribine-containing regimens combined with allo-HSCT have been proposed as a potential strategy to improve outcomes in relapsed or refractory (R/R) AML, additional clinical evidence is needed, particularly in pediatric populations. This single-center retrospective study aimed to describe the efficacy and safety of a cladribine-based conditioning regimen for allo-HSCT in children with R/R AML. Materials and Methods Clinical data of 16 children with R/R AML who underwent allo-HSCT following a cladribine-based conditioning regimen at our hospital from October 2020 to June 2024 were analyzed retrospectively. Key outcomes included hematopoietic reconstruction, regimen related toxicity (RRT), cumulative incidence of GVHD, infection profiles, OS, DFS and NRM. Flow-cytometry MRD results before HSCT were collected and analyzed as an additional key baseline index. Results: All 16 patients attained hematopoietic reconstruction, with pre-transplant flow-cytometry MRD negative in 13 cases (81.25%) and positive (MRD ≥0.01%) in 3 cases (18.75%). The median time of neutrophils and platelet engraftment were 12 (10-16) days and 15 (10-25) days respectively. The incidence of Ⅰ/Ⅱgrade RRT was 31.3%, with no Ⅲ/Ⅳgrade RRT observed. The cumulative incidence of aGVHD was 50.0%. Among 15 evaluable patients, the cumulative incidence of cGVHD was 26.7%. Post-transplant infections occurred in 31.3% of patients, predominantly viral pathogens: 1 case of BK virus-associated hemorrhagic cystitis, 1 case of BK virus combined with bacterial infection, and 3 cases of CMV DNAemia. The median follow-up time was 28.03 (11.67-55.34) months. Using the Kaplan-Meier method, the 1-year OS rate was 87.5%, and the 1-year DFS rate was 87.4%. The relapse rate and NRM were both 6.3%; the NRM case was confirmed as BOS induced by pulmonary cGVHD. Conclusions: In this small single-center retrospective series, the cladribine-based conditioning regimen was associated with favorable hematopoietic reconstruction, mild RRT, and promising survival outcomes in children with R/R AML, even in partial patients with pre-transplant MRD positivity. However, due to the limited sample size, single-arm design, and lack of a control group, conclusions regarding superiority cannot be drawn. Larger prospective multi-center studies are required to validate these preliminary findings.