Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in X-Linked Hyper IgM Syndrome: A Multicenter Chinese...

X-linked hyper-IgM syndrome (XHIGM) is a rare immunodeficiency for which allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option, yet large pediatric Chinese datasets are scarce. We retrospectively analyzed 71 boys with genetically confirmed CD40L deficiency who underwent allogeneic HSCT between 2009 and 2020 at eight centers in China. Median age at HSCT was 3 yr (range, 0.6 to 17), with 74.6% transplanted before age 5. Donors were mismatched unrelated (42.3%), matched unrelated (33.8%), matched sibling (18.3%), and haploidentical (5.6%). Peripheral blood was the predominant stem cell source (67.6%), followed by cord blood (31.0%). Myeloablative conditioning was used in 95.8%. Median times to neutrophil and platelet engraftment were 12 and 14 d, respectively. Primary graft failure occurred in 5.6%. Acute GVHD developed in 60.6% (grade III to IV, 11.3%), and chronic GVHD in 25.4% (none-severe). Cytomegalovirus and EBV-DNAemia occurred in 56.3% and 39.4%, respectively; post-transplant lymphoproliferative disorder developed in 4.2%. Other complications included sinusoidal obstruction syndrome and hemorrhagic cystitis (7.0% each). At last follow-up, 9 patients (12.1%) had died, mainly from infections (8.5%). At a median follow-up of 7.8 yr, the estimated 10-yr overall, disease-free, and GVHD-free survival rates were 85.91%, 64.79%, and 77.14%, respectively. Survival was superior in younger patients, those with lower body weight, and well-matched related or unrelated donors. Immune reconstitution showed early NK recovery with progressive T and B cell restoration over 1 yr. These data support HSCT as effective long-term therapy for XHIGM and highlight benefits of early timing and optimal HLA matching.