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.
Bibliographical noteFunding Information:
Advocate Hope Children’s Hospital Children’s Hospital of Michigan Children’s Hospital of Orange County Children’s National Medical Center Children’s Hospital of Philadelphia Cincinnati Children’s Hospital Medical Center Duke Medical Center Emory Children’s Center Immune Deficiency Foundation Levine Children’s Hospital Massachusetts General Hospital Mayo Clinic Memorial Healthcare Systems Mount Sinai Medical Center Nationwide Children’s Hospital National Institutes of Health Seattle Children’s Hospital University of Iowa Hospital University of California San Francisco University of Utah United States Immunodeficiency Network
Funding The USIDNET is supported by a cooperative agreement (U24AI86837) from the National Institute of Allergy and Infectious Diseases (NIAID)/NIH, which has been awarded to the Immune Deficiency Foundation.
Acknowledgements The United States Immunodeficiency Network (USIDNET) is supported by a cooperative agreement, U24AI86837, from the National Institute of Allergy and Infectious Diseases (NIAID)/ National Institute of Health (NIH), which has been awarded to the Immune Deficiency Foundation.
The United States Immunodeficiency Network (USIDNET) is supported by a cooperative agreement, U24AI86837, from the National Institute of Allergy and Infectious Diseases (NIAID)/National Institute of Health (NIH), which has been awarded to the Immune Deficiency Foundation. The authors would like to thank the USIDNET Steering Committee (Dr. Charlotte Cunningham-Rundles, Dr. Luigi Notarangelo, and Dr. Jennifer Puck) and Marla Goldsmith (Registry Manager) for their contributions to this work. All coauthors have reviewed this manuscript and have contributed in a substantive and intellectual manner to this work.
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
- Chronic granulomatous disease
- graft-versus-host disease
- hematopoietic stem cell transplant
- overall survival
- primary immunodeficiency