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Prospective study of a novel, radiation-free, reduced-intensity bone marrow transplantation platform for primary immunodeficiency diseases

  1. Author:
    Dimitrova, Dimana
    Gea-Banacloche, Juan
    Steinberg, Seth M
    Sadler, Jennifer L
    Hicks, Stephanie N
    Carroll, Ellen
    Wilder,Jennifer
    Parta,Mark
    Skeffington, Lauren
    Hughes, Thomas E
    Blau, Jenny E
    Broadney, Miranda M
    Rose, Jeremy J
    Hsu, Amy P
    Fletcher, Rochelle
    Nunes, Natalia S
    Yan, Xiao-Yi
    Telford, William G
    Kapoor, Veena
    Cohen, Jeffrey I
    Freeman, Alexandra F
    Garabedian, Elizabeth
    Holland, Steven M
    Lisco, Andrea
    Malech, Harry L
    Notarangelo, Luigi D
    Sereti, Irini
    Shah, Nirali N
    Uzel, Gulbu
    Zerbe, Christa S
    Fowler, Daniel H
    Gress, Ronald E
    Kanakry, Christopher G
    Kanakry, Jennifer A

  2. Author Address

    Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Mayo Clinic, Phoenix, AZ, USA., Biostatistics and Data Management Section, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA., Clinical Research Directorate/Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Bethesda, MD, USA., National Institutes of Health Clinical Center, Bethesda, MD, USA., Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA., Section on Growth and Obesity, Program in Endocrinology, Metabolism and Genetics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: jennifer.kanakry@nih.gov.,
    1. Year: 2020
    2. Date: JAN
    3. Epub Date: 2019 09 04
  2. Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
    1. 26
    2. 1
    3. Pages: 94-106
  4. Type of Article: Article
  5. ISSN: 1083-8791
  1. Abstract:

    Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, utilize alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with median hematopoietic cell transplantation-comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III-IV acute GVHD-free, graft failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells which gradually increased by day +60. The cumulative incidences of grade II-IV and grade III-IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid-responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n=2) or with unknown underlying genetic defect (n=3). All six patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients. Copyright © 2019. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.bbmt.2019.08.018
  3. PMID: 31493539
  4. View record in Web of Science®
  5. WOS: 000507718100013
  6. PII : S1083-8791(19)30558-0

Library Notes

  1. Fiscal Year: FY2019-2020
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