Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A Primary Immune Deficiency Treatment Consortium study - 03/05/24

Doi : 10.1016/j.jaci.2024.01.013

Eyal Grunebaum, MD ^a,^⁎ , Danielle E. Arnold, MD ^b, Brent Logan, PhD ^c,^d, Suhag Parikh, MD ^e,^f, Rebecca A. Marsh, MD ^g,^h,ⁱ, Linda M. Griffith, MD, PhD ^j, Kanwaldeep Mallhi, MD ^k, Deepak Chellapandian, MD, MBBS ^l, Stephanie Si Lim, MD ^m, Christin L. Deal, MD ⁿ, Neena Kapoor, MD ^o,^p, Luis Murguía-Favela, MD ^q, Emilia Liana Falcone, MD, PhD ^r,^s, Vinod K. Prasad, MD, MBBS ^t, Fabien Touzot, MD, PhD ^u, Jack J. Bleesing, MD ^g,^h, Shanmuganathan Chandrakasan, MD ^e,^f, Jennifer R. Heimall, MD ^v,^w, Jeffrey J. Bednarski, MD, PhD ^x, Larisa A. Broglie, MD ^d,^y, Hey Jin Chong, MD, PhD ⁿ, Malika Kapadia, MD ^z,^aa, Susan Prockop, MD ^z,^aa, Blachy J. Dávila Saldaña, MD ^bb,^cc, Edo Schaefer, MD ^dd, Andrea L. Bauchat, DO ^t, Pierre Teira, MD, MSc ^ee,^ff,^gg, Sharat Chandra, MD ^g,^h, Mark Parta, MD ^cc,^{^{∗
Retired; former affiliation: Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Bethesda, Md.}}, Morton J. Cowan, MD ^hh, Christopher C. Dvorak, MD ^hh, Elie Haddad, MD, PhD ^ee,^ff, Donald B. Kohn, MD ⁱⁱ, Luigi D. Notarangelo, MD ^jj, Sung-Yun Pai, MD ^b, Jennifer M. Puck, MD ^hh, Michael A. Pulsipher, MD ^kk,^ll, Troy R. Torgerson, MD, PhD ^mm, Harry L. Malech, MD ^jj,ⁿⁿ, Elizabeth M. Kang, MD ^jj,ⁿⁿ, Jennifer W. Leiding, MD ^oo
^a Division of Immunology and Allergy, Hospital for Sick Children, Toronto, Ontario, Canada
^b Immune Deficiency–Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, Md
^c Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wis
^d Center for International Blood and Marrow Transplant Research, Milwaukee, Wis
^e Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga
^f Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Ga
^g Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
^h Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
ⁱ Pharming Healthcare Inc, Warren, NJ
^j Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^k Seattle Children’s Hospital, The University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, Wash
^l Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Fla
^m Division of Pediatric Haematology and Oncology, Kapi'olani Medical Center for Women and Children, Honolulu, Hawaii
ⁿ Division of Allergy and Immunology, University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, Pittsburgh, Pa
^o Transplant and Cell Therapy Program and Laboratory, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, Calif
^p Hematology, Oncology, and Transplant and Cell Therapy, Children's Hospital Los Angeles, Los Angeles, Calif
^q Section of Hematology/Immunology, Department of Pediatrics, Alberta Children’s Hospital Calgary, Calgary, Canada
^r Center for Immunity, Inflammation and Infectious Diseases, Montreal Clinical Research Institute, Montréal, Quebec, Canada
^s Department of Medicine, Université de Montréal, Montréal, Quebec, Canada
^t Division of Pediatric Transplant and Cellular Therapy, Duke University Medical Center, Durham, NC
^u Immunology and Rheumatology Division, Department of Pediatrics, CHU Ste-justine, Universite de Montreal, Montreal, Quebec, Canada
^v Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa
^w Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa
^x Department of Pediatrics, Washington University School of Medicine, St Louis, Mo
^y Department of Pediatrics, Division of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Medical College of Wisconsin, Milwaukee
^z Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass
^aa Department of Pediatrics, Harvard Medical School, Boston, Mass
^bb Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC
^cc Division of Blood and Marrow Transplantation and Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC
^dd Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, New York Medical College, Valhalla, NY
^ee Department of Pediatrics, Immunology and Infectious Diseases, University of Montreal, Montréal, Quebec, Canada
^ff Department of Microbiology, Immunology and Infectious Diseases, Department of Pediatrics, University of Montreal, Montréal, Quebec, Canada
^gg Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montréal, Quebec, Canada
^hh Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplantation, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif
ⁱⁱ Department of Microbiology, Immunology, and Molecular Genetics; Division of Pediatric Hematology/Oncology in the Department of Pediatrics, University of California Los Angeles, Los Angeles, Calif
^jj Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^kk Pediatric Immunology and Blood and Marrow Transplant Program, University of Utah, Salt Lake City, Utah
^ll Intermountain Primary Children's Hospital, Salt Lake City, Utah
^mm Experimental Immunology, Allen Institute for Immunology, Seattle, Wash
ⁿⁿ Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^oo Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, Md

^∗Corresponding author: Eyal Grunebaum MD, Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G1X8, Canada.Division of Immunology and AllergyDepartment of PediatricsHospital for Sick Children555 University AveTorontoOntarioM5G1X8Canada

Abstract

Background

P47phox (neutrophil cytosolic factor-1) 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

We sought 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 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 per 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 per person-years (P = .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.

Conclusions

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.

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Key words : Allogeneic hematopoietic cell transplantation, chronic granulomatous disease, p47phox

Abbreviations used : CGD, DHR, GVHD, HCT, IQR, MAC, MMRD, MMUD, MRD, MUD, p47phox, Phox, PIDTC, RIC/RTC, ROA, SI, XL-CGD

Plan

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Disease burden before HCT

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Vol 153 - N° 5

P. 1423 - mai 2024 Retour au numéro

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Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A Primary Immune Deficiency Treatment Consortium study - 03/05/24

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