Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy

• Type of Material: Article
• Authors: Danielle E Arnold, National Cancer Institute, Bethesda; Deepak Chellapandian, John Hopkins All Children’s Hospital; Suhag Parikh, Emory University; Kanwaldeep Mallhi, University of Washington; Rebecca A Marsh, Cincinnati Childrens Hosp Med Ctr; Jennifer R Heimall, Childrens Hospital of Philadelphia; Debra Grossman, National Institute of Allergy and Infectious Diseases; Maria Chitty-Lopez, University of South Florida; Luis Murguia-Favela, University of Calgary; Andrew R Gennery, Newcastle University a; Farid Boulad, Mem Sloan Kettering Canc Ctr; Erin Arbuckle, Duke University; Morton J Cowan, University of California San Francisco; Christopher C Dvorak, University of California San Francisco; Linda M Griffith, National Institute of Allergy and Infectious Diseases, Bethesda; Elie Haddad, University of Montreal; Donald B Kohn, University of California Los Angeles; Luigi D Notarangelo, National Institute of Allergy and Infectious Diseases, Bethesda; Sung-Yun Pai, National Cancer Institute, Bethesda; Jennifer M Puck, University of California San Francisco; Michael A Pulsipher, University of Southern California; Troy Torgerson, Allen Institute; Elizabeth M Kang, National Institute of Allergy and Infectious Diseases, Bethesda; Harry L Malech, National Institute of Allergy and Infectious Diseases, Bethesda; Jennifer W Leiding, Johns Hopkins University
• Language: English
• Date: 2022-04-21
• Publisher: SPRINGER/PLENUM PUBLISHERS
• Publication Version: Final Published Version
• Copyright Statement: © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022
• Final Published Version (URL): http://dx.doi.org/10.1007/s10875-022-01261-1
• Title of Journal or Parent Work: JOURNAL OF CLINICAL IMMUNOLOGY
• Volume: 42
• Issue: 5
• Start Page: 1026
• End Page: 1035
• Grant/Funding Information: The PIDTC is supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD; Public Health Service grant/cooperative agreements U54-AI082973 (MPI: JM Puck, CC Dvorak, E Haddad), U54-NS064808 and U01-TR001263 (PI: JP Krischer); and the Division of Intramural Research, NIAID, NIH. DE Arnold and SY Pai are supported by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research. The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS.
• Keywords: PEDIATRIC-PATIENTS; Hematopoietic cell transplantation; Alloimmunization; INVASIVE ASPERGILLOSIS; Chronic granulomatous disease; Science & Technology; INFECTIONS; ALLOIMMUNIZATION; Granulocyte transfusions; Graft failure; Immunology; Life Sciences & Biomedicine; DONORS
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology; Biology, Microbiology

Abstract

Granulocyte transfusions are sometimes used as adjunctive therapy for the treatment of infection in patients with chronic granulomatous disease (CGD). However, granulocyte transfusions can be associated with a high rate of alloimmunization, and their role in CGD patients undergoing hematopoietic cell transplantation (HCT) or gene therapy (GT) is unknown. We identified 27 patients with CGD who received granulocyte transfusions pre- (within 6 months) and/or post-HCT or GT in a retrospective survey. Twelve patients received granulocyte transfusions as a bridge to cellular therapy. Six (50%) of these patients had a complete or partial response. However, six of 10 (60%) patients for whom testing was performed developed anti-HLA antibodies, and three of the patients also had severe immune-mediated cytopenia within the first 100 days post-HCT or GT. Fifteen patients received granulocyte transfusions post-HCT only. HLA antibodies were not checked for any of these 15 patients, but there were no cases of early immune-mediated cytopenia. Out of 25 patients who underwent HCT, there were 5 (20%) cases of primary graft failure. Three of the patients with primary graft failure had received granulocyte transfusions pre-HCT and were subsequently found to have anti-HLA antibodies. In this small cohort of patients with CGD, granulocyte transfusions pre-HCT or GT were associated with high rates of alloimmunization, primary graft failure, and early severe immune-mediated cytopenia post-HCT or GT. Granulocyte transfusions post-HCT do not appear to confer an increased risk of graft failure.