The Role of Hematopoietic Cell Transplantation in Ataxia-Telangiectasia

Ataxia-telangiectasia (A-T) is a DNA repair disorder characterized by neurodegeneration, immunodeficiency, and cancer predisposition. Hematopoietic cell transplantation (HCT) is an established therapy in related disorders such as Fanconi anemia (FA) and Nijmegen breakage syndrome (NBS), but its role in A-T is unclear. This comprehensive review describes the current literature exploring the indications for HCT in A-T, focusing on conditioning regimens, outcomes, and toxicities.

A literature review of published A-T HCT cases and preclinical studies was performed, analyzing conditioning regimens, immune reconstitution, complications, overall survival, and follow-up.

To date, 15 patients with A-T who underwent HCT have been reported. Reduced-intensity or FA-adapted regimens were generally well tolerated and led to durable immune reconstitution, whereas myeloablative conditioning was associated with significant treatment-related toxicities, including veno-occlusive disease (VOD), graft-versus-host disease (GvHD), and hepatic failure. These clinical observations are supported by preclinical Atm-deficient mouse models demonstrating restoration of immune function and reduced lymphoma risk following HCT. Experience from related disorders, such as FA and NBS, further supports the use of radiation-sparing, fludarabine-based conditioning approaches in A-T.

The use of HCT for the treatment of immunodeficiency and relapsed/refractory hematologic malignancies in patients with A-T is not well described and understood. Current evidence is limited and heterogeneous, supporting its use only in select high-risk patients at specialized centers, with multicenter collaboration needed to define best practices.