Meta-analysis of HSCT with treosulfan in Ataxia Telangiectasia patients shows mixed survival outcomes and significant toxicities.

There is a lack of clinical data on hematopoietic stem cell transplantation (HSCT) in Ataxia-Telangiectasia (A-T) patients due to the underlying chromosomal instability that leads to low tolerance to chemotherapy. To effectively manage cancer and immune risks, there is a need for improved HSCT protocols, novel therapies, and long-term monitoring. This report describes a 16-year-old boy with A-T and T-ALL who achieved long-term leukemia-free survival after HSCT using a tailored, drug-monitored conditioning regimen. His results were analyzed in the context of a systematic review of the literature on HSCT outcomes in A-T patients. A thorough literature review was conducted using a comprehensive search of the PubMed, Scopus, and Google Scholar databases. The search was limited to studies published between September 1, 2000, and September 1, 2025. Eligible studies were required to involve human participants and to include at least one patient with a confirmed diagnosis of A-T, with transplantation interventions. The analysis included 16 A-T patients, including our patient, who underwent HSCT. The median age at transplantation was 48 months (interquartile range [IQR]: 22–142 months). Myeloablative conditioning (MAC) was administered to two patients, both of whom died. Reduced-intensity conditioning (RIC) was utilized for nine patients, with three deaths (33.3%). Reduced-toxicity conditioning (RTC) was administered in two patients, with one patient experiencing a fatal outcome. In total, eight patients (50%) experienced significant drug-related toxicities, eight (50%) had GvHD and only eight patients (50%) survived. Our patient underwent HSCT of a matched sibling donor after administration of adjusted treosulfan doses (cumulative AUC of 4671 mg/Lxh), and achieved leukemia-free survival with complete hematological and normalized thymic function without graft-versus-host disease (GvHD). Despite the historically poor survival outcomes observed in transplanted A-T patients, new HSCT strategies, such as treosulfan therapeutic drug monitoring and personalized drug profiles to select potent but less toxic agents, warrant reevaluation to achieve durable remission in leukemia and lymphoma. These findings underscore the necessity to persist in the development of innovative HSCT approaches with the objective of expanding therapeutic options for both malignancies and combined immunodeficiency.