Abstract
The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD41 and CD41CD45RA1 cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD41 cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.
Original language | English (US) |
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Pages (from-to) | 1737-1749 |
Number of pages | 13 |
Journal | Blood |
Volume | 132 |
Issue number | 17 |
DOIs | |
State | Published - Oct 25 2018 |
Funding
This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID) and the 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), and R13-AI094943 (M.J.C.); and the Division of Intramural Research, NIAID, NIH. The PIDTC is a part of the Rare Diseases Clinical Research Network of ORDR, NCATS. Collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium is supported by the U54 grants above, along with support from the Pediatric Blood and Marrow Transplant Consortium Operations Center by the St. Baldrick’s Foundation and grant/cooperative agreement U10HL069254 (PI: M.A.P.) from the National Heart, Lung and Blood Institute (NHLBI) and the National Cancer Institute (NCI), NIH. Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research is supported by grant/cooperative agreement U24-CA76518 (PI: M.M. Horowitz) from the NCI, NHLBI, and NIAID, NIH and grant/cooperative agreement U01HL069294 from the NHLBI and NCI, NIH; contracts HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration/Department of Health and Human Services; and grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research.
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology