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Multicenter Study
. 2024 May;153(5):1423-1431.e2.
doi: 10.1016/j.jaci.2024.01.013. Epub 2024 Jan 28.

Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A Primary Immune Deficiency Treatment Consortium study

Eyal Grunebaum  1 , Danielle E Arnold  2 , Brent Logan  3 , Suhag Parikh  4 , Rebecca A Marsh  5 , Linda M Griffith  6 , Kanwaldeep Mallhi  7 , Deepak Chellapandian  8 , Stephanie Si Lim  9 , Christin L Deal  10 , Neena Kapoor  11 , Luis Murguía-Favela  12 , Emilia Liana Falcone  13 , Vinod K Prasad  14 , Fabien Touzot  15 , Jack J Bleesing  16 , Shanmuganathan Chandrakasan  4 , Jennifer R Heimall  17 , Jeffrey J Bednarski  18 , Larisa A Broglie  19 , Hey Jin Chong  10 , Malika Kapadia  20 , Susan Prockop  20 , Blachy J Dávila Saldaña  21 , Edo Schaefer  22 , Andrea L Bauchat  14 , Pierre Teira  23 , Sharat Chandra  16 , Mark Parta  24 , Morton J Cowan  25 , Christopher C Dvorak  25 , Elie Haddad  26 , Donald B Kohn  27 , Luigi D Notarangelo  28 , Sung-Yun Pai  2 , Jennifer M Puck  25 , Michael A Pulsipher  29 , Troy R Torgerson  30 , Harry L Malech  31 , Elizabeth M Kang  31 , Jennifer W Leiding  32
Affiliations
Multicenter Study

Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A Primary Immune Deficiency Treatment Consortium study

Eyal Grunebaum et al. J Allergy Clin Immunol. 2024 May.

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.

Keywords: Allogeneic hematopoietic cell transplantation; chronic granulomatous disease; p47phox.

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Conflict of interest statement

Disclosure of potential conflict of interest:

E. Grunebaum is an author for UpToDate and a consultant for Prime Medicine. R. A. Marsh is an author for UpToDate, an employee of Pharming Healthcare Inc and a consultant for Horizon Therapeutics. L. Murguía-Favela is on the Data Safety Monitoring Committee for Encoded Therapeutics. J. J. Bleesing is an author for UpToDate. E. L. Falcone has done advisory activities for Bruker Corporation. J. Heimall is an author for UpToDate, received an investigator-initiated grant from CSL Behring, and is a consultant for ADMA, CIRM, and Horizon. S. Prockop receives support for the conduct of sponsored trials from AlloVir and Jasper, and is a consultant for CellEvolve, Century, Pierre Fabre, and VOR Bio. S. Prockop received honoraria from Regeneron. B. J. Dávila Saldaña is on the Data Safety Monitoring Board for Orchard Therapeutics, and consultant for Sobi. M. J. Cowan is an author for UpToDate and is on the Data Safety Monitoring Board for Chiesi, Inc., Rocket Pharmaceuticals and Bluebird Bio. C. C. Dvorak is an author for UpToDate, is on the Data Safety Monitoring Board for Chiesi, and consultant for Orchard Therapeutics. E. Haddad is on the Data Safety Monitoring Board for Jasper and Rocket Pharma, and is a consultant for Prime Medicine, Takeda, and Octaphrama. O D. B. Kohn is an author for UpTo Date, is on the Data Safety Monitoring Board for Chiesi, and is a consultant/Scientific Advisory Board (SAB) member for ImmunoVec. J. M. Puck is an editor and author for UpToDate. M. A. Pulsipher reports study support from Adaptive and Miltenyi, working as an advisor for Vertex, Medexus, Equillium, Novartis, and Mesoblast, and receives educational honoraria from Novartis and Miltenyi. H. L. Malech serves without compensation as consultant/Scientific Advisory Board member for Jasper Therapeutics, Emendo Biotherapeutics, Orpha Labs, Ensoma, ImmunoVec, Curate Bio, and the DADA2 Foundation; as an advisor to and with Cooperative Research and Development Agreement support from CSL Behring and from Prime Medicine; and as Chair of an Independent Data Monitoring Committee for Rocket Pharmaceuticals. T. R. Torgerson is a consultant for Pharming Healthcare and is a member of the independent data safety monitoring board for Takeda. Other authors declare that they have no relevant conflicts of interest.

Figures

Figure 1.
Figure 1.. Disease burden in patients with p47phox CGD receiving allogenic hematopoietic cell transplantation.
a. Infections in patients with p47phox CGD. The density (per person years) of all infections, CGD-related infections, and fungal infections, in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant. b. Antimicrobial prophylaxis in patients with p47phox CGD. The percent of patients receiving antibacterial and anti-fungal prophylaxis in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant. c. Inflammation in patients with p47phox CGD. The percent of patients suffering from inflammatory disease, non-infectious lung disease and inflammatory bowel disease, and using systemic corticosteroids in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant.
Figure 1.
Figure 1.. Disease burden in patients with p47phox CGD receiving allogenic hematopoietic cell transplantation.
a. Infections in patients with p47phox CGD. The density (per person years) of all infections, CGD-related infections, and fungal infections, in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant. b. Antimicrobial prophylaxis in patients with p47phox CGD. The percent of patients receiving antibacterial and anti-fungal prophylaxis in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant. c. Inflammation in patients with p47phox CGD. The percent of patients suffering from inflammatory disease, non-infectious lung disease and inflammatory bowel disease, and using systemic corticosteroids in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant.
Figure 1.
Figure 1.. Disease burden in patients with p47phox CGD receiving allogenic hematopoietic cell transplantation.
a. Infections in patients with p47phox CGD. The density (per person years) of all infections, CGD-related infections, and fungal infections, in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant. b. Antimicrobial prophylaxis in patients with p47phox CGD. The percent of patients receiving antibacterial and anti-fungal prophylaxis in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant. c. Inflammation in patients with p47phox CGD. The percent of patients suffering from inflammatory disease, non-infectious lung disease and inflammatory bowel disease, and using systemic corticosteroids in the year before hematopoietic cell transplantation (HCT), as well as 1 year and 2 years after HCT. NS= Not statistically significant.
Figure 2.
Figure 2.. Outcome after hematopoietic cell transplantation for p47phox CGD
a. Graft failure and/or receipt of second hematopoietic cell transplantation (HCT). The cumulative incidence of graft failure and/or receipt of a second HCT after HCT is shown. HCT, hematopoietic cell transplant. b. Overall and event-free survival after hematopoietic cell transplantation (HCT). The probability of (A) overall and event-free survival post-HCT after HCT are shown. An event was defined as death, graft failure or second HCT. HCT, hematopoietic cell transplant; EFS, event free survival; OS, overall survival.
Figure 2.
Figure 2.. Outcome after hematopoietic cell transplantation for p47phox CGD
a. Graft failure and/or receipt of second hematopoietic cell transplantation (HCT). The cumulative incidence of graft failure and/or receipt of a second HCT after HCT is shown. HCT, hematopoietic cell transplant. b. Overall and event-free survival after hematopoietic cell transplantation (HCT). The probability of (A) overall and event-free survival post-HCT after HCT are shown. An event was defined as death, graft failure or second HCT. HCT, hematopoietic cell transplant; EFS, event free survival; OS, overall survival.
Figure 3.
Figure 3.. Donor chimerism after hematopoietic cell transplantation for p47phox CGD
The distribution of patients with p47phox CGD who had 0–10%, 11–50%, 51–94, or 95–100% donor chimerism in whole blood, myeloid cells, or T cells, at 1 and 2 years after hematopoietic cell transplantation.
See this image and copyright information in PMC

References

    1. Leiding JW, Holland SM. Chronic Granulomatous Disease. 2012 Aug 9 [updated 2022 Apr 21]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. - PubMed
    1. Roos D, van Leeuwen K, Hsu AP, Priel DL, Begtrup A, Brandon R, et al. Hematologically important mutations: The autosomal forms of chronic granulomatous disease (third update). Blood Cells Mol Dis. 2021. Dec;92:102596. Doi: 10.1016/j.bcmd.2021.102596. - DOI - PubMed
    1. van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PloS One. 2009;4(4):e5234. Doi: 10.1371/journal.pone.0005234. Epub 2009 Apr 21. - DOI - PMC - PubMed
    1. Rawat A, Vignesh P, Sudhakar M, Sharma M, Suri D, Jindal A, et al. Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India. Front Immunol. 2021. Feb 25;12:625320. Doi: 10.3389/fimmu.2021.625320. - DOI - PMC - PubMed
    1. Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010. 363(27):2600–10. Doi: 10.1056/NEJMoa1007097. - DOI - PMC - PubMed

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