Chronic granulomatous disease (CGD) can be cured by allogeneic haemopoietic stem-cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GvHD), infection and transplant-related mortality (TRM); therefore, reduced-intensity conditioning (RIC) regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of Treosulfan-based conditioning in HSCT for paediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GvHD, chimerism, viral reactivation, post-HSCT complications, length of follow up and outcome. Seventy patients (median age 107 months; IQR 46-232) from 16 centres worldwide were transplanted between 2006 and 2015. Ninety-one % had high-risk features. Fifty-seven HLA-matched donor, 12 HLA-mismatched donor and 1 CD3+TCR alpha beta/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR15-35) and 16 (IQR13-50) days. At a median follow-up of 34 months (IQR13-102), the overall survival was 91.4% and EFS was 81.4%. The cumulative incidence of acute grade III-IV GvHD was 12%. Nine patients developed chronic GvHD. When split cell chimerism was available, ≥95% myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft-failure occurred in 12% of patients. Treosulfan containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome particularly on fertility.
