Clinical picture of boys with XSCID and the road to gene therapy

Abstract

X-Linked Severe Combined Immune Deficiency is a rare (about 1/50 000) disorder manifested by a lack of both cellular and humoral immune function. Without treatment the affected male infants usually die in their first year of life from persistent and chronic infections, particularly with opportunistic pathogens. Treatment by bone marrow transplantation (BMT) rescues > 90% of the patients fortunate enough to have an HLA matched sibling donor. Survival is decreased to 60–80% if the donor is a parent whose HLA antigens match half of the child’s. However, short and long-term complications of BMT include graft failure, graft versus host disease and lack of B-cell reconstitution, leaving patients dependent on monthly IV gammaglobulin infusions. We have evaluated eight males between the ages of 5–19 who were selected because of poor outcome after BMT. They all have growth failure, malabsorption, lung disease, and chronic anemia. They all have received 1–4 haploidentical BMTs but continue to be on monthly IVIG and antibiotics. Because their T cell counts are falling and are insufficient to regulate immune response, they are candidates to enrol in the NIH XSCID Gene Transfer clinical trial. This presentation will describe the clinical picture of the eight gene transfer candidates and how the treated subject progressed after receiving gene transfer.