Jennifer R Yonkof1, Ashish Gupta1, Pingfu Fu2, Elizabeth Garabedian3, Jignesh Dalal4. 1. Cleveland Medical Center, Department of Pediatric Hematology-Oncology, Rainbow Babies and Children's Hospital, 11100 Euclid Ave., Cleveland, OH, 44106, USA. 2. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Wood Bldg., Rm. WG-82P, 2109 Adelbert Rd., Cleveland, OH, 44106, USA. 3. National Institutes of Health, National Human Genome Research Institute, Bldg. 10/10C-103, MSC 1611, 10 Center Dr., Bethesda, MD, 20892, USA. 4. Cleveland Medical Center, Department of Pediatric Hematology-Oncology, Rainbow Babies and Children's Hospital, 11100 Euclid Ave., Cleveland, OH, 44106, USA. Jignesh.Dalal@UHhospitals.org.
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.
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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