J Clin Immunol. 2026 Mar 28. doi: 10.1007/s10875-026-02008-y. Online ahead of print.
ABSTRACT
PURPOSE: Congenital athymia is a life-threatening condition characterized by thymic absence and profound T-cell immunodeficiency. Thymus implantation is the definitive treatment, but its availability is limited. This study aimed to evaluate the outcomes of hematopoietic cell transplantation (HCT) as an alternative therapy.
METHODS: A nationwide, multicenter, retrospective study analyzed nine patients who underwent allogeneic HCT between 2000 and 2024 in Japan. Overall survival (OS) was estimated using the Kaplan-Meier method, and the cumulative incidence of immunodeficiency-related mortality was assessed using Gray’s test.
RESULTS: Among the nine patients, eight (89%) received umbilical cord blood, and one (11%) received related peripheral blood. Seven patients (78%) underwent transplantation without conditioning. Engraftment with T-cell recovery was achieved in six patients (67%), with a median CD4+ T-cell count of 0.352 × 109/L (range, 0.216-1.578 × 109/L) at the last follow-up. Acute graft-versus-host disease (GVHD) occurred in five patients (56%), all with Grade I-II skin involvement. No chronic GVHD was observed. The one-year OS rate was 66.7% (95% confidence interval: 28.2%-87.8%). Overall, six patients (67%) died: three early deaths within the first month from infections, and three late deaths beyond 1 year from congenital comorbidities. HCT before six months of age was associated with significantly lower immunodeficiency-related mortality (p = 0.02).
CONCLUSION: HCT can allow immune reconstitution in congenital athymia, although long-term survival is affected by comorbidities. Early diagnosis and timely intervention are crucial in managing this condition. HCT can be a restricted alternative therapy for patients ineligible for thymus implantation.
PMID:41902846 | DOI:10.1007/s10875-026-02008-y