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Systematic Review of Hematopoietic Stem Cell Transplantation in Ataxia Telangiectasia: Case Repo

Systematic review of hematopoietic stem cell transplantation in ataxia telangiectasia, including a case of leukemia-free survival after tailored conditioning and drug monitoring.

GIST

BackgroundThere 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.MethodsA 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.ResultsThe 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).

Clinical Editorial

Theme-driven appraisal of HSCT in Ataxia-Telangiectasia: a focused case within a broader synthesis: Context and purpose: - The report addresses hematopoietic stem cell transplantation (HSCT) in Ataxia-Telangiectasia (A-T), noting chromosomal instability that confers low chemotherapy tolerance. - The study presents a 16-year-old male with A-T and T-ALL who achieved long-term leukemia-free survival after a tailored conditioning regimen, analyzed alongside a systematic literature review of HSCT outcomes in A-T patients. Study design and methods: - A literature search spanned PubMed, Scopus, and Google Scholar for records from September 1, 2000, to September 1, 2025, focusing on human studies with at least one A-T patient undergoing HSCT. - Data extraction centered on patient characteristics, conditioning regimens, toxicity, graft-versus-host disease (GvHD), and survival outcomes, enabling an individual patient-level synthesis. Population and conditioning exposure: - The aggregated cohort comprised 16 A-T patients who underwent HSCT. - Median age at transplantation was 48 months, with an IQR of 22–142 months. - Conditioning strategies varied: myeloablative conditioning (MAC) in two patients (both fatal), reduced-intensity conditioning (RIC) in nine (three deaths, 33.3%), and reduced-toxicity conditioning (RTC) in two (one fatal outcome). - Across the cohort, eight patients (50%) encountered significant drug-related toxicities, eight (50%) developed GvHD, and eight (50%) survived. Key single-patient signal and case-specific observations: - The featured case involved a matched sibling donor HSCT with adjusted treosulfan dosing guided by drug exposure monitoring (cumulative AUC 4671 mg/L×h). - The patient achieved leukemia-free survival with complete hematologic recovery and normalization of thymic function, without GvHD. Context within the evidence landscape: - Historically, survival after HSCT in A-T has been limited, with prior outcomes described as poor. - The current synthesis highlights potential signals of benefit from conditioning personalization, particularly treosulfan-based approaches coupled with pharmacokinetic/pharmacodynamic monitoring to balance efficacy and toxicity. Operational implications and uncertainties: - The data suggest that tailored conditioning regimens, including drug monitoring to modulate exposure, may influence tolerability and remission durability in A-T with hematologic malignancies. - Limitations include small sample size (n=16), heterogeneous conditioning protocols, and incomplete uniform reporting of long-term outcomes and functional measures. - Uncertainty remains regarding reproducibility, optimal dosing targets, and the generalizability of single-case successes to broader A-T populations. Open questions and future directions: - Prospective studies are needed to define standardized, low-toxicity conditioning frameworks suitable for A-T.

Original source: https://www.frontiersin.org/articles/10.3389/fimmu.2026.1754093