Role of Allogeneic Hematopoietic Stem Cell Transplant for Chronic Granulomatous Disease (CGD): a Report of the United States Immunodeficiency Network

and the United States Immunodeficiency Network Consortium

Research output: Contribution to journalArticle

Abstract

Purpose: Chronic granulomatous disease (CGD) is a primary immunodeficiency for which allogeneic hematopoietic stem cell transplant (HSCT) offers potential cure. Direct comparison of HSCT to non-HSCT management in the North American population was performed to identify clinical factors associated with overall survival (OS) and transplant-related survival (TRS). Methods: Retrospective review of CGD subjects enrolled in the United States Immunodeficiency Network. Survival was estimated by the Kaplan-Meier method and modeled by proportional hazards regression. Results: We identified 507 patients (66% CYBB mutants) diagnosed in 1953–2016. Fifty underwent allogeneic HSCT. Median follow-up was 9.1 years after diagnosis (0–45.8 years). OS was negatively associated with CYBB mutation (HR = 6.25; p = 0.034) and not associated with HSCT (88% v. 85% ± HCT) (HR = 1.26; p = 0.65). Transplant at ≤ 14 years old was associated with improved TRS (93% v. 82% at T + 60 months) (HR = − 4.51; p = 0.035). Patients transplanted before 15 years old had fewer severe infections pre-HSCT (mean 0.95 v. 2.13; p = 0.047). No mortality was reported in patients receiving stem cells from matched siblings. Infection incidence declined post-HSCT in subjects with greater than or equal to four infections pre-HSCT (p = 0.0010). Compared to non-HSCT patients ≥ 15 years old, post-transplant survivors had higher mean performance score (93.2 v. 85.9; p = 0.0039) and lower frequency of disability (11% v. 52%; p = 0.014). Conclusion: Allogeneic HSCT was associated with reduced infection incidence and improved functional performance, but not with a change in overall survival. Transplant-related survival was elevated in patients undergoing HSCT before 15 years old. Consider HSCT prior to late adolescence in patients with severely diminished reactive oxygen intermediate synthesis, particularly if a matched sibling is available.

Original languageEnglish (US)
Pages (from-to)448-458
Number of pages11
JournalJournal of Clinical Immunology
Volume39
Issue number4
DOIs
StatePublished - May 15 2019

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Chronic Granulomatous Disease
Hematopoietic Stem Cells
Transplants
Survival
Stem Cells
Infection
Siblings

Keywords

  • Chronic granulomatous disease
  • USIDNET
  • graft-versus-host disease
  • hematopoietic stem cell transplant
  • overall survival
  • primary immunodeficiency

PubMed: MeSH publication types

  • Journal Article

Cite this

Role of Allogeneic Hematopoietic Stem Cell Transplant for Chronic Granulomatous Disease (CGD) : a Report of the United States Immunodeficiency Network. / and the United States Immunodeficiency Network Consortium.

In: Journal of Clinical Immunology, Vol. 39, No. 4, 15.05.2019, p. 448-458.

Research output: Contribution to journalArticle

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title = "Role of Allogeneic Hematopoietic Stem Cell Transplant for Chronic Granulomatous Disease (CGD): a Report of the United States Immunodeficiency Network",
abstract = "Purpose: Chronic granulomatous disease (CGD) is a primary immunodeficiency for which allogeneic hematopoietic stem cell transplant (HSCT) offers potential cure. Direct comparison of HSCT to non-HSCT management in the North American population was performed to identify clinical factors associated with overall survival (OS) and transplant-related survival (TRS). Methods: Retrospective review of CGD subjects enrolled in the United States Immunodeficiency Network. Survival was estimated by the Kaplan-Meier method and modeled by proportional hazards regression. Results: We identified 507 patients (66{\%} CYBB mutants) diagnosed in 1953–2016. Fifty underwent allogeneic HSCT. Median follow-up was 9.1 years after diagnosis (0–45.8 years). OS was negatively associated with CYBB mutation (HR = 6.25; p = 0.034) and not associated with HSCT (88{\%} v. 85{\%} ± HCT) (HR = 1.26; p = 0.65). Transplant at ≤ 14 years old was associated with improved TRS (93{\%} v. 82{\%} at T + 60 months) (HR = − 4.51; p = 0.035). Patients transplanted before 15 years old had fewer severe infections pre-HSCT (mean 0.95 v. 2.13; p = 0.047). No mortality was reported in patients receiving stem cells from matched siblings. Infection incidence declined post-HSCT in subjects with greater than or equal to four infections pre-HSCT (p = 0.0010). Compared to non-HSCT patients ≥ 15 years old, post-transplant survivors had higher mean performance score (93.2 v. 85.9; p = 0.0039) and lower frequency of disability (11{\%} v. 52{\%}; p = 0.014). Conclusion: Allogeneic HSCT was associated with reduced infection incidence and improved functional performance, but not with a change in overall survival. Transplant-related survival was elevated in patients undergoing HSCT before 15 years old. Consider HSCT prior to late adolescence in patients with severely diminished reactive oxygen intermediate synthesis, particularly if a matched sibling is available.",
keywords = "Chronic granulomatous disease, USIDNET, graft-versus-host disease, hematopoietic stem cell transplant, overall survival, primary immunodeficiency",
author = "{and the United States Immunodeficiency Network Consortium} and Yonkof, {Jennifer R.} and Gupta, {Ashish O} and Pingfu Fu and Elizabeth Garabedian and Jignesh Dalal",
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AU - Gupta, Ashish O

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AU - Garabedian, Elizabeth

AU - Dalal, Jignesh

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N2 - Purpose: Chronic granulomatous disease (CGD) is a primary immunodeficiency for which allogeneic hematopoietic stem cell transplant (HSCT) offers potential cure. Direct comparison of HSCT to non-HSCT management in the North American population was performed to identify clinical factors associated with overall survival (OS) and transplant-related survival (TRS). Methods: Retrospective review of CGD subjects enrolled in the United States Immunodeficiency Network. Survival was estimated by the Kaplan-Meier method and modeled by proportional hazards regression. Results: We identified 507 patients (66% CYBB mutants) diagnosed in 1953–2016. Fifty underwent allogeneic HSCT. Median follow-up was 9.1 years after diagnosis (0–45.8 years). OS was negatively associated with CYBB mutation (HR = 6.25; p = 0.034) and not associated with HSCT (88% v. 85% ± HCT) (HR = 1.26; p = 0.65). Transplant at ≤ 14 years old was associated with improved TRS (93% v. 82% at T + 60 months) (HR = − 4.51; p = 0.035). Patients transplanted before 15 years old had fewer severe infections pre-HSCT (mean 0.95 v. 2.13; p = 0.047). No mortality was reported in patients receiving stem cells from matched siblings. Infection incidence declined post-HSCT in subjects with greater than or equal to four infections pre-HSCT (p = 0.0010). Compared to non-HSCT patients ≥ 15 years old, post-transplant survivors had higher mean performance score (93.2 v. 85.9; p = 0.0039) and lower frequency of disability (11% v. 52%; p = 0.014). Conclusion: Allogeneic HSCT was associated with reduced infection incidence and improved functional performance, but not with a change in overall survival. Transplant-related survival was elevated in patients undergoing HSCT before 15 years old. Consider HSCT prior to late adolescence in patients with severely diminished reactive oxygen intermediate synthesis, particularly if a matched sibling is available.

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