Transplantation outcomes for severe combined immunodeficiency, 2000-2009 Journal Article


Authors: Pai, S. Y.; Logan, B. R.; Griffith, L. M.; Buckley, R. H.; Parrott, R. E.; Dvorak, C. C.; Kapoor, N.; Hanson, I. C.; Filipovich, A. H.; Jyonouchi, S.; Sullivan, K. E.; Small, T. N.; Burroughs, L.; Skoda-Smith, S.; Haight, A. E.; Grizzle, A.; Pulsipher, M. A.; Chan, K. W.; Fuleihan, R. L.; Haddad, E.; Loechelt, B.; Aquino, V. M.; Gillio, A.; Davis, J.; Knutsen, A.; Smith, A. R.; Moore, T. B.; Schroeder, M. L.; Goldman, F. D.; Connelly, J. A.; Porteus, M. H.; Xiang, Q.; Shearer, W. T.; Fleisher, T. A.; Kohn, D. B.; Puck, J. M.; Notarangelo, L. D.; Cowan, M. J.; O'Reilly, R. J.
Article Title: 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 pretransplantation 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.) Copyright © 2014 Massachusetts Medical Society.
Keywords: controlled study; treatment outcome; survival rate; retrospective studies; major clinical study; fludarabine; lymphocyte proliferation; antigens, cd3; t-lymphocytes; incidence; genetic variability; cyclophosphamide; immunoglobulin; hematopoietic stem cell transplantation; transplantation; retrospective study; siblings; b lymphocyte; survival time; myeloablative conditioning; nonmyeloablative conditioning; whole body radiation; infant; cd4+ t lymphocyte; graft versus host reaction; transplantation conditioning; cd4 lymphocyte count; t cell depletion; cd3+ t lymphocyte; immunosuppressive treatment; graft vs host disease; immunoglobulin blood level; severe combined immunodeficiency; retreatment; alemtuzumab; lymphocyte count; genetic heterogeneity; thymocyte antibody; immunoglobulin a; pneumocystis jiroveci; humans; human; male; female; priority journal; article; membrane reconstitution
Journal Title: New England Journal of Medicine
Volume: 371
Issue: 5
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2014-07-31
Start Page: 434
End Page: 446
Language: English
DOI: 10.1056/NEJMoa1401177
PUBMED: 25075835
PROVIDER: scopus
PMCID: 25075835
DOI/URL:
Notes: Export Date: 2 September 2014 -- CODEN: NEJMA -- Source: Scopus
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  1. Trudy Small
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  2. Richard O'Reilly
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