Treatment for X-Linked Agammaglobulinemia with Allogeneic Umbilical Cord Blood Stem Cell Transplantation from HLA-Matched Sibling Confirmed Healthy through Prenatal Diagnosis

Background X-linked agammaglobulinemia (XLA) is a rare congenital humoral immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19⁺ B-cells which was caused by mutations in Bruton's tyrosine kinase (BTK). We herein describe the first case of XLA transplanted from HLA-matched sibling allogeneic umbilical cord blood donor.

Method The patient was an 8-year-old boy with XLA who previously had life-threatening infectious episodes and diagnosed by direct sequencing of BTK gene mutations (c.992-923delGAN(NM-000061)) when he was 3 years old. He was treated with the regular replacement of immunoglobulin G (IgG) products. Taking into consideration significant infectious complications and the prompt availability of HLA-matched sibling umbilical cord blood, he underwent HLA-matched sibling UCBT. The FC conditioning regimen consisting of Flu (30mg/m²/d×4 days) and CTX (30mg/kg/d×4 days) was provided for the patient. The source of stem cells was umbilical cord blood of his younger brother who was confirmed completely healthy through prenatal diagnosis with villi at the fetus period of 4 months. The number of infused total nucleated and CD34+ cells was 6.51×10⁸/L and 2.67×10⁶/L, respectively. He received a combination of CsA, short-term MTX and MMF for GVHD prophylaxis.

Result Hematopoietic engraftment was rapidly achieved, with an absolute neutrophil count of >0.5×10⁹/L on day 15 and platelet count of >20×10⁹/L on day 20. The patient was discharged on day 45 and has been followed as an outpatient without any infectious episodes for more than 180 days. No expected toxicities were observed. Regarding immune constitution, CD19+ cells, IgA and IgM, which were undetectable before transplantation, started to increase in number 10 days after transplantation and continued to increase for more than 3 months. The patient did not exhibit any GVHD manifestations. He is currently alive and doing well at six months post-transplant, and he is free of any infection episodes.

Conclusion The above results provide strong evidence that HLA-matched sibling UCBT may be safe and technically feasible for the treatment of XLA when an appropriately matched related or unrelated donor is unavailable. The umbilical cord blood could be considered being frozen, especially in the era of "the second child" in China.

Keywords X-linked agammaglobulinemia; HLA-matched sibling donor; allogeneic umbilical cord blood stem cell transplantation; immune recovery.