Genotype, oxidase status, and preceding infection or autoinflammation do not affect allogeneic HCT outcomes for CGD

Jennifer W. Leiding, Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD.
Danielle E. Arnold, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Suhag Parikh, Aflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, Atlanta, GA.
Brent Logan, Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
Rebecca A. Marsh, Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.
Linda M. Griffith, Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Ruizhe Wu, Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
Sharon Kidd, Pediatric Allergy, Immunology, and Blood and Marrow Transplant Division, UCSF Benioff Children's Hospital, San Francisco, CA.
Kanwaldeep Mallhi, Fred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington, and Seattle Children's Hospital, Seattle, WA.
Deepak Chellapandian, Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, FL.
Stephanie J. Si Lim, Department of Pediatrics, John A. Burns School of Medicine, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI.
Eyal Grunebaum, Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
E Liana Falcone, Center for Inflammation, Immunity and Infectious Diseases, Montreal Clinical Research Institute, Montreal, QC, Canada.
Luis Murguia-Favela, Section of Hematology/Immunology, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
Debbi Grossman, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Vinod K. Prasad, Division of Pediatric Transplant and Cellular Therapy, Department of Pediatrics, Duke University Medical Center, Durham, NC.
Jennifer R. Heimall, Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
Fabien Touzot, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, Canada.
Lauri M. Burroughs, Fred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington, and Seattle Children's Hospital, Seattle, WA.
Jack Bleesing, Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.
Neena Kapoor, Division of Hematology, Oncology and Blood and Marrow Transplant, Children's Hospital, Los Angeles, CA.
Jasmeen Dara, Pediatric Allergy, Immunology, and Blood and Marrow Transplant Division, UCSF Benioff Children's Hospital, San Francisco, CA.
Olatundun Williams, Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Malika Kapadia, Division of Hematology-Oncology, Boston Children's Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Benjamin R. Oshrine, Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, FL.
Jeffrey J. Bednarski, Washington University, St. Louis Children's Hospital, St. Louis, MO.
Ahmad Rayes, Division of Pediatric Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute at the University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT.
Hey Chong, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA.
Geoffrey D. Cuvelier, Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
Lisa R. Forbes Satter, Immunology, Allergy and Retrovirology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.
Caridad Martinez, Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital Center for Gene and Cell Therapy, Houston, TX.
Mark T. Vander Lugt, Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI.

Document Type

Journal Article

Publication Date

12-14-2023

Journal

Blood

Volume

142

Issue

24

DOI

10.1182/blood.2022019586

Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score <90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.

Department

Pediatrics

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