Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009

Abstract

BACKGROUND The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. METHODS We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). RESULTS Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell–depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pre-transplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin-induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. CONCLUSIONS Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Mini Review: Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogeneic Hematopoietic Cell Transplantation

“…B-SCID genotypes, active infection at time of HCT, and graft-versus-host disease (GVHD) are all associated with poor T cell recovery 3,7,8,17 . Evaluation of T cell reconstitution should include enumeration of T cell populations (i.e., CD3, CD4 and CD8 T cell counts), naïve (CD4+CD45RA+) T cells and/or recent thymic emigrants (CD4+/CD45RA+/CD31+), and T cell function via proliferation to mitogens and/or anti-CD3.…”

“…There are few large studies reporting on late effects following transplantation for SCID 7,11,13,33 . Prospective studies are needed to investigate long-term survival and quality of life, immune reconstitution, need for stem cell boost or second transplantation, and rates of GVHD by SCID genotype and phenotype, donor source, graft manipulation, and conditioning regimen.…”

“…The first successful hematopoietic cell transplantation (HCT) for SCID was performed in 1968, and allogeneic HCT remains the standard of care for SCID today. Outcomes are greatly improved with early transplantation in the first 3.5 months of life and particularly before onset of infection, with reported survival rates of 80% to 95% regardless of donor source or conditioning [1][2][3][4][5][6][7][8] . Newborn screening for SCID was first initiated in Wisconsin in 2008, and today, 93% of all newborns in the US receive SCID screening 9,10 .…”

“…The use of conditioning before HCT for SCID remains controversial and varies by transplant center, donor type, clinical presentation, and SCID genotype. Preparative conditioning has been associated with greater likelihood of myeloid engraftment, long-term T cell reconstitution, and freedom from immunoglobulin replacement 7,8,[11][12][13][14] . However, the long-term consequences of using chemotherapeutic agents in early infancy remain incompletely understood.…”

HSCT: How Does It Work?

“…For many patients with PID, partial donor chimaerism is sufficient to induce cure if the affected recipient cell lineage is replaced completely or partially by donor cells, although complete donor chimaerism is best in some diseases (Gennery 2015). Pai et al (2014) reported the results of 240 infants who received a transplant for SCID, at 25 centres in the USA between January 2000 and December 2009. The overall survival rate at 5 years was 74%; most deaths were within the first year after transplant and were due to infections (39%) or pulmonary complications (37%).…”