Prognosis

Without treatment, early mortality usually occurs in the first year of life. Early and accurate diagnosis, in conjunction with early treatment, improves overall survival in patients with SCID. A review of registry data from the European Blood and Marrow Transplant Network and the Center for International Blood and Marrow Transplantation showed that underlying genotype and immunophenotype, in conjunction with early transplantation, predict early survival.[46]

Haematopoietic stem cell transplantation

Overall survival rates of approximately 95% have been reported in patients who undergo haematopoietic stem cell transplantation (HSCT) for SCID within the first 3.5 months of life.[8][10] Human leukocyte antigen (HLA)-matched related grafts are the treatment of choice, but most patients do not have this option available.

A study from the Primary Immune Deficiency Treatment Consortium collected data from 240 patients with SCID who received HSCT at 25 different transplant centres between 2000 and 2009. Transplantation prior to 3.5 months of age was associated with a 5-year survival rate of 94%.[10] Five-year survival was greatest among those patients who received transplants from matched sibling donors (97%); the comparable figure for patients receiving grafts from unrelated donors was 58% to 79% (depending on graft source and T-cell depletion).[10]

Data from a European series following 475 patients from 1968 to 1999 have shown 3-year survival rates for all SCID phenotypes to be 80% for matched sibling donors.[46][63] Survival rates for SCID patients who received transplants from unrelated matched donors were lower at 70%, and transplants from HLA-unmatched donors were lowest at 50%.[46][63] In the absence of a related HLA-matched donor, unrelated HLA-matched donor grafts result in better immune reconstitution and clinical outcomes than from a mismatched related donor.[50] A study of 338 patients with SCID who received HSCT from 2006 to 2014 showed a 2-year overall survival of 81.1%, with no differences among SCID genotypes.[64] Outcomes for adenosine deaminase deficient SCID (ADA-SCID) have been particularly favourable in recent years. A retrospective case series of 33 patients with ADA-SCID who received HSCT between 1989 and 2020 reported an overall survival at 8 years of 90.9% (95% CI 79.7 to 100.0%), with an overall survival after 2007 (n=21) of 100%.[65]

Enzyme replacement therapy

Long-term outcomes in patients treated with pegylated adenosine deaminase (PEG-ADA) have not been prospectively studied, but immune reconstitution appears to be variable.[54] In a European cohort, continued immunoglobulin replacement was required in 40% of patients treated with PEG-ADA for one year, and overall survival among those who received PEG-ADA alone (i.e., no HSCT) was 85%.[55] Patients receiving enzyme replacement therapy for ADA-deficient SCID gradually develop decreased levels of T cells, B cells, and natural killer cells with sub-optimal proliferative responses.[53]

Patients with adenosine deaminase deficiency SCID are often started on enzyme replacement therapy with the goal of proceeding to HSCT if a matched sibling or family donor is available.[12]

Use of this content is subject to our disclaimer