Outcome of hematopoietic stem cell transplantation for adenosine deaminase deficient severe combined immunodeficiency

Deficiency of the purine salvage enzyme adenosine deaminase leads to severe combined immunodeficiency (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to permanent cure of SCID, however little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSD, MFD) had significantly better overall survival (OS) (86% and 81%) in comparison to HCT from matched unrelated (66%; p<0.05) and haploidentical donors (43%; p<0.0001). Superior OS was also seen in patients who received unconditioned transplants in comparison to myeloablative procedures (81% vs 54%; p<0.003) although in unconditioned haploidentical donor HCT, non-engraftment was a major problem. Long term immune recovery showed that regardless of transplant type, overall T cell numbers were similar although a faster rate of T cell recovery was observed following MSD/MFD HCT. Humoral immunity and donor B cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and demonstrate that if patients survive HCT, long term cellular and humoral immune recovery is achieved