The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treatedwith allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patientswith typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survivalwas 90%, but was 95%for thosewhowere infection-free at HCTvs 81%for those withactive infection (P5.009). Other factors, including thediagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, useofpreparative chemotherapy,or thetypeof donorused,did not impact survival.Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day 1100 post-HCT revealed that CD3 < 300 cells/mL, CD8 < 50 cells/mL, CD45RA < 10%, or a restricted Vb T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free.
Bibliographical noteFunding Information:
This work was supported by Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Public Health Service grant/ cooperative agreements U54-AI082973 (principal investigator [PI]: M.J.C.), U54-NS064808 and U01-TR001263 (PI: J. P. Krischer),