Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: a PIDTC study

Eyal Grunebaum, Division of Immunology and Allergy, Hospital for Sick Children, Toronto, ON, Canada. Electronic address: eyal.grunebaum@sickkids.ca.
Danielle E. Arnold, Immune Deficiency - Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Brent Logan, Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI; Center for International Blood and Marrow Transplant Research Milwaukee, WI.
Suhag Parikh, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
Rebecca A. Marsh, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Pharming Healthcare Inc, Warren, NJ.
Linda M. Griffith, Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Kanwaldeep Mallhi, Seattle Children's Hospital, The University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA.
Deepak Chellapandian, Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL.
Stephanie Si Lim, Division of Pediatric Haematology and Oncology, Kapi'olani Medical Center for Women & Children, Hawaii, HI.
Christin L. Deal, Division of Allergy and Immunology, UPMC, Children's Hospital of Pittsburgh, Pittsburgh, PA.
Neena Kapoor, Transplant and Cell Therapy Program and Laboratory, Department of Pediatrics, Keck School of Medicine, University of Southern California, CA; Hematology, Oncology and Transplant and Cell Therapy, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Luis Murguía-Favela, Section of Hematology/Immunology, Department of Pediatrics, Alberta Children's Hospital Calgary, Calgary, AB, Canada.
Emilia Liana Falcone, Center for Immunity, Inflammation and Infectious Diseases, Montreal Clinical Research Institute (IRCM), Montreal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Vinod K. Prasad, Division of Pediatric Transplant and Cellular Therapy, Duke University Medical Center, Durham, NC.
Fabien Touzot, Immunology and Rheumatology Division, Department of Pediatrics, CHU Ste-Justine, Montréal, Québec, Canada.
Jack J. Bleesing, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Shanmuganathan Chandrakasan, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
Jennifer R. Heimall, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, PA; Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA.
Jeffrey J. Bednarski, Department of Pediatrics, Washington University School of Medicine, St Louis, MO.
Larisa A. Broglie, Center for International Blood and Marrow Transplant Research, Milwaukee, WI; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.
Hey Jin Chong, Division of Allergy and Immunology, UPMC, Children's Hospital of Pittsburgh, Pittsburgh, PA.
Malika Kapadia, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA.
Susan Prockop, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA.
Blachy J. Dávila Saldaña, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington DC; Division of Blood and Marrow Transplantation and Center for Cancer and Immunology Research, Children's National Hospital, Washington DC.
Edo Schaefer, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, New York Medical College, Valhalla, NY.
Andrea L. Bauchat, Division of Pediatric Transplant and Cellular Therapy, Duke University Medical Center, Durham, NC.
Pierre Teira, Department of Pediatrics and Department of Microbiology, Immunology and Infectious Diseases, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada; Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
Sharat Chandra, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Mark Parta, Retired, formerly Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Bethesda, MA.
Morton J. Cowan, Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplantation, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA.
Christopher C. Dvorak, Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplantation, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA.
Elie Haddad, Department of Pediatrics and Department of Microbiology, Immunology and Infectious Diseases, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.

Document Type

Journal Article

Publication Date

1-28-2024

Journal

The Journal of allergy and clinical immunology

DOI

10.1016/j.jaci.2024.01.013

Keywords

Allogeneic hematopoietic cell transplantation; Chronic granulomatous disease; p47phox

Abstract

BACKGROUND: P47phox deficiency is the most common cause of autosomal recessive chronic granulomatous disease (CGD) and is considered to be associated with a milder clinical phenotype. Allogeneic hematopoietic cell transplantation (HCT) for p47phox CGD is not well-described. OBJECTIVES: To study HCT for p47phox CGD in North America. METHODS: Thirty patients with p47phox CGD who received allogeneic HCT at Primary Immune Deficiency Treatment Consortium (PIDTC) centers since 1995 were included. RESULTS: Residual oxidative activity was present in 66.7% of patients. In the year before HCT, there were 0.38 CGD-related infections/person-years. Inflammatory diseases, predominantly of the lungs and bowel, occurred in 36.7% of the patients. The median age at HCT was 9.1 years (range 1.5-23.6 years). Most HCTs (90%) were performed after using reduced intensity/toxicity conditioning. HCT sources were HLA-matched (40%) and -mismatched (10%) related donors, or HLA-matched (36.7%) and -mismatched (13.3%) unrelated donors. CGD-related infections after HCT decreased significantly to 0.06/person-years (p=0.038). The frequency of inflammatory bowel disease and the use of steroids also decreased. The cumulative incidence of graft failure and second HCT was 17.9%. The 2-year overall and event-free survival were 92.3% and 82.1%, respectively, while at 5 years they were 85.7% and 77.0%, respectively. In the surviving patients evaluated, >95% donor myeloid chimerism at 1 and 2 years after HCT was 93.8% and 87.5%, respectively. CONCLUSION: Patients with p47phox CGD suffer from a significant disease burden that can be effectively alleviated by HCT. Similar to other forms of CGD, HCT should be considered for patients with p47phox CGD.

Department

Pediatrics

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