Faculty Collaboration Database

Allogeneic hematopoietic cell transplantation is effective for p47phox chronic granulomatous disease: A  Primary Immune Deficiency Treatment Consortium study. J Allergy Clin Immunol 2024 May;153(5):1423-1431.e2

Date

01/31/2024

Pubmed ID

38290608

Pubmed Central ID

PMC11070290

DOI

10.1016/j.jaci.2024.01.013

Scopus ID

2-s2.0-85185611997 (requires institutional sign-in at Scopus site)

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.

Author List

Grunebaum E, Arnold DE, Logan B, Parikh S, Marsh RA, Griffith LM, Mallhi K, Chellapandian D, Lim SS, Deal CL, Kapoor N, Murguía-Favela L, Falcone EL, Prasad VK, Touzot F, Bleesing JJ, Chandrakasan S, Heimall JR, Bednarski JJ, Broglie LA, Chong HJ, Kapadia M, Prockop S, Dávila Saldaña BJ, Schaefer E, Bauchat AL, Teira P, Chandra S, Parta M, Cowan MJ, Dvorak CC, Haddad E, Kohn DB, Notarangelo LD, Pai SY, Puck JM, Pulsipher MA, Torgerson TR, Malech HL, Kang EM, Leiding JW

Authors

Larisa Broglie MD, MS Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Child
Child, Preschool
Female
Graft vs Host Disease
Granulomatous Disease, Chronic
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
NADPH Oxidases
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome
Young Adult