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The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901

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Abstract

The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1–2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.

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Acknowledgements

This paper is dedicated to the memory of Dr. Trudy Small, a gifted physician who dedicated her life to improving transplant outcomes for children with immunodeficiencies. The authors thank Elizabeth Dunn and Jessica Carlson for their tireless efforts organizing the PIDTC, Yanning Wang for expert technical assistance from the UCSF core lab, and Mary Eapen, MD and Qun Xiang from the CIBMTR for assistance with data analysis. Data collection for this study were in-part facilitated through the CIBMTR (U24-CA76518; PI Horowitz MM). The PIDTC is a part of NIH Rare Diseases Clinical Research Network, with the DMCC at the University of South Florida. Portions of this data were presented as an oral abstract at the annual meeting of the American Society for Blood and Marrow Transplant, Salt Lake City, UT, 14 February 2013 (abstract no. 93). Funding and/or programmatic support for this project has been provided by Grant #1U54AI082973 from National Institute of Allergy and Infectious Diseases and the NIH Office of Rare Diseases Research, National Center for Advancing Translational Science. The views expressed are those of the authors and do not represent the position of the NIAID, ORDR/NCATS, NIH, or the US Government.

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Pediatric Allergy, Immunology, and Bone Marrow Transplant, Benioff Children’s Hospital, University of California San Francisco, 505 Parnassus Ave., M-659, San Francisco, CA, 94143-1278, USA

    Christopher C. Dvorak, Morton J. Cowan & Jennifer M. Puck

  2. Division of Biostatistics, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    Brent R. Logan

  3. Division of Immunology and The Manton Center for Orphan Disease Research, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

    Luigi D. Notarangelo

  4. Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MA, USA

    Linda M. Griffith

  5. Departments of Microbiology, Immunology & Molecular Genetics and Pediatrics, University of California Los Angeles, Los Angeles, CA, USA

    Donald B. Kohn

  6. Departments of Pediatrics and Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA

    William T. Shearer & I. Celine Hanson

  7. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Richard J. O’Reilly & Trudy Small

  8. Department of Laboratory Medicine, National Institutes of Health, Bethesda, MA, USA

    Thomas A. Fleisher

  9. Division of Hematology and Oncology, Boston Children’s Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Sung-Yun Pai

  10. Division of Hematology and Hematologic Malignancies, Primary Children’s Medical Center, University of Utah School of Medicine/Huntsman Cancer Institute, Salt Lake City, UT, USA

    Michael A. Pulsipher

  11. Division of Allergy and Immunology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Ramsay Fuleihan

  12. Division of Hematology/Oncolog, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Alexandra Filipovich

  13. Division of Hematology and Oncology, The Children’s Hospital of Alabama, University of Alabama, Tuscaloosa, AL, USA

    Frederick Goldman

  14. Division of Research Immunology and Bone Marrow Transplantation, Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    Neena Kapoor

  15. Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA

    Angela Smith

  16. Pediatric Stem Cell Transplantation Program, Texas Transplant Institute, San Antonio, TX, USA

    Ka-Wah Chan

  17. Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada

    Geoff Cuvelier

  18. Division of Allergy/Immunology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jennifer Heimall

  19. Division of Pediatric Allergy & Immunology, St. Louis University, St Louis, MO, USA

    Alan Knutsen

  20. Blood and Marrow Transplantation, Allergy and Immunology, Children’s National Medical Center, Washington, DC, USA

    Brett Loechelt

  21. Division of Pediatric Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA

    Theodore Moore

  22. Departments of Pediatrics & Immunology, Duke University Medical Center, Durham, NC, USA

    Rebecca H. Buckley

Authors
  1. Christopher C. Dvorak
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  2. Morton J. Cowan
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  3. Brent R. Logan
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  4. Luigi D. Notarangelo
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  5. Linda M. Griffith
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  6. Jennifer M. Puck
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  7. Donald B. Kohn
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  8. William T. Shearer
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  9. Richard J. O’Reilly
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  10. Thomas A. Fleisher
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  11. Sung-Yun Pai
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  12. I. Celine Hanson
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  13. Michael A. Pulsipher
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  14. Ramsay Fuleihan
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  15. Alexandra Filipovich
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  16. Frederick Goldman
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  17. Neena Kapoor
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  18. Trudy Small
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  19. Angela Smith
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  20. Ka-Wah Chan
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  21. Geoff Cuvelier
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  22. Jennifer Heimall
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  23. Alan Knutsen
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  24. Brett Loechelt
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  25. Theodore Moore
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  26. Rebecca H. Buckley
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Corresponding author

Correspondence to Christopher C. Dvorak.

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Dvorak, C.C., Cowan, M.J., Logan, B.R. et al. The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901. J Clin Immunol 33, 1156–1164 (2013). https://doi.org/10.1007/s10875-013-9917-y

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  • DOI: https://doi.org/10.1007/s10875-013-9917-y

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