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 (original) (raw)
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
- 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 - Division of Biostatistics, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA
Brent R. Logan - Division of Immunology and The Manton Center for Orphan Disease Research, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA
Luigi D. Notarangelo - Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MA, USA
Linda M. Griffith - Departments of Microbiology, Immunology & Molecular Genetics and Pediatrics, University of California Los Angeles, Los Angeles, CA, USA
Donald B. Kohn - Departments of Pediatrics and Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
William T. Shearer & I. Celine Hanson - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Richard J. O’Reilly & Trudy Small - Department of Laboratory Medicine, National Institutes of Health, Bethesda, MA, USA
Thomas A. Fleisher - Division of Hematology and Oncology, Boston Children’s Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Sung-Yun Pai - 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 - 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 - Division of Hematology/Oncolog, Cincinnati Children’s Hospital, Cincinnati, OH, USA
Alexandra Filipovich - Division of Hematology and Oncology, The Children’s Hospital of Alabama, University of Alabama, Tuscaloosa, AL, USA
Frederick Goldman - Division of Research Immunology and Bone Marrow Transplantation, Children’s Hospital of Los Angeles, Los Angeles, CA, USA
Neena Kapoor - Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA
Angela Smith - Pediatric Stem Cell Transplantation Program, Texas Transplant Institute, San Antonio, TX, USA
Ka-Wah Chan - Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
Geoff Cuvelier - Division of Allergy/Immunology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jennifer Heimall - Division of Pediatric Allergy & Immunology, St. Louis University, St Louis, MO, USA
Alan Knutsen - Blood and Marrow Transplantation, Allergy and Immunology, Children’s National Medical Center, Washington, DC, USA
Brett Loechelt - Division of Pediatric Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA
Theodore Moore - Departments of Pediatrics & Immunology, Duke University Medical Center, Durham, NC, USA
Rebecca H. Buckley
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- Christopher C. Dvorak
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Correspondence toChristopher 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
- Received: 27 February 2013
- Accepted: 10 June 2013
- Published: 02 July 2013
- Issue Date: October 2013
- DOI: https://doi.org/10.1007/s10875-013-9917-y