Treatment for severe combined immunodeficiency (SCID) in the era of newborn screening (NBS)

Abstract

Abstract SCID is associated with excellent survival when treated with allogeneic hematopoietic cell transplantation (HCT), gene therapy (GT), or enzyme replacement therapy (ERT) within 3–4 months of birth or prior to infection. NBS for SCID results in the diagnosis by 2–3 weeks of age. This retrospective analysis describes therapy and immune reconstitution of 28 infants diagnosed by NBS in California since 2010 and treated at the University of California, San Francisco at a median of 56 (24–217) days of age. HCT with alkylating chemotherapy (N=6), serotherapy alone (N=6), or no conditioning (N=12) was used in 24 infants, and ERT followed by definitive GT at University of California, Los Angeles, was used in 4 ADA-deficient infants. Overall survival at >2 years was 93% with 1 death from HHV6 and 1 from CMV. The median time to CD4 T cell recovery (>200 T cells/uL) was 73 (10–96) days for ERT patients prior to GT, and 138 days (14–220) for HCT patients. Time from first appearance of donor chimerism to CD4 recovery was evaluable for 14 HCT survivors who lacked pre-HCT maternal chimerism or whose donors were not their mothers. After donor chimerism appeared in peripheral blood at a median of 21.5 (14–169) days, appearance of T cells took 32 (0–84) more days. Second transplant or stem cell boost was required for 10 of 24 patients at a median of 77 (35–382) days following first HCT; for patients eligible for analysis (N=15), need for 2nd therapy was significantly higher in those without detectable donor chimerism by 28 days following therapy (0% vs 83%, p=0.04). NBS for SCID allowed rapid institution of anti-infective and definitive treatment to optimize outcomes, and early detection of donor chimerism was associated with successful T cell recovery.