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

Authors

• 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.

APA Citation

Grunebaum, Eyal; Arnold, Danielle E.; Logan, Brent; Parikh, Suhag; Marsh, Rebecca A.; Griffith, Linda M.; Mallhi, Kanwaldeep; Chellapandian, Deepak; Lim, Stephanie Si; Deal, Christin L.; Kapoor, Neena; Murguía-Favela, Luis; Falcone, Emilia Liana; Prasad, Vinod K.; Touzot, Fabien; Bleesing, Jack J.; Chandrakasan, Shanmuganathan; Heimall, Jennifer R.; Bednarski, Jeffrey J.; Broglie, Larisa A.; Chong, Hey Jin; Kapadia, Malika; Prockop, Susan; Dávila Saldaña, Blachy J.; Schaefer, Edo; Bauchat, Andrea L.; Teira, Pierre; Chandra, Sharat; Parta, Mark; Cowan, Morton J.; Dvorak, Christopher C.; and Haddad, Elie, "Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: a PIDTC study" (2024). GW Authored Works. Paper 4114.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4114

Department

Pediatrics