REDUCED toxicity conditioning demonstrated encouraging outcomes for children with X linked hyper IgM syndrome undergoing allogeneic haematopoietic cell transplantation, according to a retrospective review of 10 patients treated at a single institution.
X linked hyper IgM syndrome is an inherited error of immunity caused by variants in the CD40LG gene, resulting in impaired T cell function and defective immunoglobulin class switch recombination. Supportive care alone has been associated with poor outcomes, making allogeneic haematopoietic cell transplantation the only curative treatment. Although myeloablative conditioning has been recommended before transplantation, concerns remain regarding treatment related toxicity.
The investigators reviewed outcomes for 10 patients with X linked hyper IgM syndrome who underwent transplantation between 2010 and 2024 using a reduced toxicity conditioning regimen. All patients received transplantation by 5 years of age, with ages ranging from 2–5 years and a median age of 3 years. Donor sources included unrelated bone marrow, unrelated cord blood, and haploidentical related donors.
Conditioning predominantly consisted of fludarabine and busulfan, targeting an area under the curve of 60–65 mg/L·h. Low dose total body irradiation was incorporated into the conditioning regimen for five patients.
Two patients experienced graft failure and subsequently required a second transplantation. One patient died because of post-transplant complications, while the remaining nine patients survived. The reported 5-year overall survival rate was 88.9%, and the 5-year graft versus host disease free, relapse free, and second transplantation free survival rate was 67.5%.
The investigators also observed that adding low dose total body irradiation to fludarabine and busulfan was associated with favourable long-term donor chimerism.
The authors noted that the observed association between low dose total body irradiation and improved donor chimerism should be regarded as hypothesis generating. Nevertheless, the overall findings suggested that reduced toxicity conditioning may provide an effective alternative to conventional myeloablative conditioning for patients with X linked hyper IgM syndrome undergoing allogeneic haematopoietic cell transplantation.
Although further evaluation will be required to confirm these findings, the results indicated that reduced toxicity conditioning could offer a feasible approach that balances successful engraftment with reduced treatment related toxicity in this rare inherited immune disorder.
Reference
Wakatsuki R et al. Allogeneic hematopoietic cell transplantation with reduced-toxicity conditioning for X-linked hyper-IgM syndrome. Int J Hematol. 2026;DOI:10.1007/s12185-026-04245-8.
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