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

Theme-driven appraisal of HSCT in Ataxia-Telangiectasia: a focused case within a broader synthesis:

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Prospective studies are needed to define standardized, low-toxicity conditioning frameworks suitable for A-T.