The Journal of Allergy and Clinical Immunology
Volume 122, Issue 6 , Pages 1087-1096, December 2008

Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: Current status and critical needs

  • Linda M. Griffith, MD, PhD

      Affiliations

    • Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
    • ,
  • Morton J. Cowan, MD

      Affiliations

    • Pediatric Blood and Marrow Transplant Division, UCSF Children's Hospital, San Francisco, Calif
    • ,
  • Donald B. Kohn, MD

      Affiliations

    • Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, Calif
    • ,
  • Luigi D. Notarangelo, MD

      Affiliations

    • Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Mass
    • ,
  • Jennifer M. Puck, MD

      Affiliations

    • Department of Pediatrics, Institute for Human Genetics, University of California San Francisco, San Francisco, Calif
    • ,
  • Kirk R. Schultz, MD

      Affiliations

    • Pediatric Blood and Marrow Transplantation, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Rebecca H. Buckley, MD

      Affiliations

    • Pediatric Allergy and Immunology, Duke University School of Medicine, Durham, NC
    • ,
  • Mary Eapen, MD, MS

      Affiliations

    • Center for International Blood and Marrow Transplant Research/Medical College of Wisconsin, Milwaukee, Wis
    • ,
  • Naynesh R. Kamani, MD

      Affiliations

    • Blood and Marrow Transplantation and Immunology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC
    • ,
  • Richard J. O'Reilly, MD

      Affiliations

    • Departments of Pediatrics and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY
    • ,
  • Robertson Parkman, MD

      Affiliations

    • Division of Research Immunology/BMT, Childrens Hospital Los Angeles, Los Angeles, Calif
    • ,
  • Chaim M. Roifman, MD, FRCPC

      Affiliations

    • Division of Immunology and Allergy, the Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    • ,
  • Kathleen E. Sullivan, MD, PhD

      Affiliations

    • Pediatric Immunology, Children's Hospital of Philadelphia, University of Pennsylvania, Pennsylvania, Pa
    • ,
  • Alexandra H. Filipovich, MD

      Affiliations

    • Pediatric Clinical Immunology, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    • ,
  • Thomas A. Fleisher, MD

      Affiliations

    • Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Md
    • ,
  • William T. Shearer, MD, PhD

      Affiliations

    • Pediatric Allergy and Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex
    • Corresponding Author InformationReprint requests: William T. Shearer, MD, PhD, Department of Allergy and Immunology, Texas Children's Hospital, Baylor College of Medicine, MC FC330.01, 6621 Fannin St, Ste A-380, Houston TX, 77030-2399.
    • ,
  • workshop participants

Received 29 August 2008; received in revised form 11 September 2008; accepted 15 September 2008. published online 07 November 2008.

Allogeneic hematopoietic cell transplantation (HCT) has been used for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, including severe combined immunodeficiency (SCID) and non-SCID PID. There is a critical need for evaluation of the North American experience of different HCT approaches for these diseases to identify best practices and plan future investigative clinical trials. Our survey of incidence and prevalence of PID in North American practice sites indicates that such studies are feasible. A conference of experts in HCT treatment of PID has recommended (1) a comprehensive cross-sectional and retrospective analysis of HCT survivors with SCID; (2) a prospective study of patients with SCID receiving HCT, with comparable baseline and follow-up testing across participating centers; (3) a pilot study of newborn screening for SCID to identify affected infants before compromise by infection; and (4) studies of the natural history of disease in patients who do or do not receive HCT for the non-SCID diseases of Wiskott-Aldrich syndrome and chronic granulomatous disease. To accomplish these goals, collaboration by a consortium of institutions in North America is proposed. Participation of immunologists and HCT physicians having interest in PID and experts in laboratory methods, clinical outcomes assessment, databases, and analysis will be required for the success of these studies.

Key words: Allogeneic hematopoietic cell transplantation, primary immune deficiency, clinical trial

Abbreviations used: ADA, Adenosine deaminase, BMT, Bone marrow transplantation, CGD, Chronic granulomatous disease, CIBMTR, Center for International Blood and Marrow Transplant Research, CID, Combined immunodeficiency, GVHD, Graft-versus-host disease, HCT, Hematopoietic (stem) cell transplantation, NK, Natural killer, PEG-ADA, Polyethylene glycol adenosine deaminase, PID, Primary immune deficiency, SCID, Severe combined immunodeficiency, TCR, T-cell receptor, USIDNET, United States Immunodeficiency Network, WAS, Wiskott-Aldrich syndrome

 

 Disclosure of potential conflict of interest: M. J. Cowan has received research support from the March of Dimes and Enzo Therapeutics. J. M. Puck has received research support from USIDNET and has provided legal consultation on primary immunodeficiency. K. R. Schultz has received research support from the National Cancer Institute and the Leukemia and Lymphoma Society and has served as an expert witness for DOIL BioPharma. R. H. Buckley has received research support from the National Institutes of Health. N. R. Kamani has received research support from the Pediatric Blood and Marrow Transplant Consortium/Children's Oncology Group and has served as a member of the National Marrow Donor Program. R. J. O'Reilly has received research support from the National Institutes of Health and owns stock in Calibrant. R. Parkman has received research support from the National Institutes of Health. K. E. Sullivan has received research support from the National Institutes of Health and USIDNET, has served as an expert witness for Contocor-Psorusis, and has consulting arrangements with the Immune Deficiency Foundation. The rest of the authors have declared that they have no conflict of interest.

 Report of a workshop sponsored by the Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, and the Office of Rare Diseases, National Institutes of Health, Bethesda, Md, May 12-13, 2008.

 The opinions expressed are those of the authors and do not represent the position of the National Institute of Allergy and Infectious Diseases, the Office of Rare Diseases, the National Institutes of Health, or the US Government.

PII: S0091-6749(08)01841-1

doi:10.1016/j.jaci.2008.09.045

The Journal of Allergy and Clinical Immunology
Volume 122, Issue 6 , Pages 1087-1096, December 2008

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