[Unrelated umbilical cord blood stem cell transplantation in the treatment of hyper-IgM syndrome caused by CD40 ligand gene mutation: a report of three cases and literature review].

ABSTRACT

Objective: To evaluate the efficacy and safety of unrelated umbilical cord blood stem cell transplantation (UCBT) with reduced-intensity conditioning regimens in the treatment of hyper-IgM syndrome (HIGM) caused by CD40 ligand gene (CD40LG) mutation. Methods: Clinical features, laboratory data and treatment prognosis of 3 patients with HIGM caused by CD40LG mutation treated with UCBT in Children's Hospital of Fudan University from May 2018 to August 2019 were analyzed retrospectively. The literature search was conducted with "CD40 ligand deficiency" and "hematopoietic stem cell transplantation" as keywords at China National Knowledge Infrastructure, Wanfang, Weipu and Pubmed databases (up to February 2021) to summarize donor selection, stem cell source, conditioning regimen and prognostic factors of this disease. Results: Three boys with recurrent respiratory tract infection were diagnosed as HIGM with CD40LG mutation. The age of UCBT was 1.0, 1.4 and 0.5 years respectively. Reduced-intensity conditioning regimen including busulifan, fludarabine and cyclophosphamide were used in all patients. Human leucocyte antigen matching of patients and umbilical cord blood was 8/10, 10/10 and 9/10 respectively. All patients achieved complete donor chimerism 14 days after UCBT. All patient suffered grade Ⅰ acute skin graft-versus-host disease without other severe complications. Up to the last follow-up, their disease-free survival time were 33, 18, 18 months after transplantation respectively. No reports were found in Chinese journals, while 24 publications were found in English journals. According to the literature, 258 HIGM patients with CD40LG mutation were treated with hematopoietic stem cell transplantation (HSCT). Matched sibling donors (30.6%(79/258)) and unrelated donors (40.3% (104/258)) were main donor types. Bone marrow (50.8%(131/258)) was the main source of grafts, myeloablative conditioning (66.7% (172/258)) was the main conditioning regimen, and the overall survival rate after transplantation was 70.9% (183/258). Lung injury and liver complications before transplantation were adverse factors affecting prognosis. Among the 14 patients who received UCBT, 2 patients suffered from engraftment failure, 2 patients had mixed chimerism and 3 patients died after transplantation. Conclusions: UCBT is safe and effective in the treatment of HIGM caused by CD40LG mutation. Reduced-intensity conditioning regimen is worthy of further study.