Cinzia Dedieu1,2, Michael H Albert3, Nizar Mahlaoui4, Fabian Hauck3, Christian Hedrich5,6, Ulrich Baumann7, Klaus Warnatz8, Joachim Roesler5, Carsten Speckmann8,9, Johannes Schulte2, Alain Fischer4, Stephane Blanche4, Horst von Bernuth1,10,11, Jörn-Sven Kühl2,12. 1. Department of Pediatric Pneumology, Immunology and Intensive Care, Charité Universitätsmedizin, Berlin University Hospital Center, Berlin, Germany. 2. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Charité Universitätsmedizin -Berlin University Hospital Center, Berlin, Germany. 3. Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. 4. Pediatric Hematology-Immunology Unit, AP-HP, Necker Hospital, Paris, France. 5. Department of Pediatrics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany. 6. Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool and Department of Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK. 7. Department of Pediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany. 8. Center of Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 9. Center of Pediatrics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 10. Department of Immunology, Labor Berlin GmbH, Berlin, Germany. 11. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany. 12. Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cure chronic granulomatous disease (CGD), but it remains debated whether all conventionally treated CGD patients benefit from HSCT. METHODS: We retrospectively analyzed 104 conventionally treated CGD patients, of whom 50 patients underwent HSCT. RESULTS: On conventional treatment, seven patients (13%) died after a median time of 16.2 years (interquartile range [IQR] 7.0-18.0). Survival without severe complications was 10 ± 3% (mean ± SD) at the age of 20 years; 85% of patients developed at least one infection, 76% one non-infectious inflammation. After HSCT, 44 patients (88%) were alive at a median follow-up of 2.3 years (IQR 0.8-4.9): Six patients (12%) died from infections. Survival after HSCT was significantly better for patients transplanted ≤8 years (96 ± 4%) or for patients without active complications at HSCT (100%). Eight patients suffered from graft failure (16%); six (12%) developed acute graft-vs-host disease requiring systemic treatment. Conventionally treated patients developed events that required medical attention at a median frequency of 1.7 (IQR 0.8-3.2) events per year vs 0 (IQR 0.0-0.5) in patients beyond the first year post-HSCT. While most conventionally treated CGD patients failed to thrive, catch-up growth after HSCT in surviving patients reached the individual percentiles at the age of diagnosis of CGD. CONCLUSION: Chronic granulomatous disease patients undergoing HSCT until 8 years of age show excellent survival, but young children need more intense conditioning to avoid graft rejection. Risks and benefits of HSCT for adolescents and adults must still be weighed carefully.
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cure chronic granulomatous disease (CGD), but it remains debated whether all conventionally treated CGD patients benefit from HSCT. METHODS: We retrospectively analyzed 104 conventionally treated CGD patients, of whom 50 patients underwent HSCT. RESULTS: On conventional treatment, seven patients (13%) died after a median time of 16.2 years (interquartile range [IQR] 7.0-18.0). Survival without severe complications was 10 ± 3% (mean ± SD) at the age of 20 years; 85% of patients developed at least one infection, 76% one non-infectious inflammation. After HSCT, 44 patients (88%) were alive at a median follow-up of 2.3 years (IQR 0.8-4.9): Six patients (12%) died from infections. Survival after HSCT was significantly better for patients transplanted ≤8 years (96 ± 4%) or for patients without active complications at HSCT (100%). Eight patients suffered from graft failure (16%); six (12%) developed acute graft-vs-host disease requiring systemic treatment. Conventionally treated patients developed events that required medical attention at a median frequency of 1.7 (IQR 0.8-3.2) events per year vs 0 (IQR 0.0-0.5) in patients beyond the first year post-HSCT. While most conventionally treated CGD patients failed to thrive, catch-up growth after HSCT in surviving patients reached the individual percentiles at the age of diagnosis of CGD. CONCLUSION:Chronic granulomatous diseasepatients undergoing HSCT until 8 years of age show excellent survival, but young children need more intense conditioning to avoid graft rejection. Risks and benefits of HSCT for adolescents and adults must still be weighed carefully.
Authors: Xiao Chen; Dongdong Wang; Jianger Lan; Guangfei Wang; Lin Zhu; Xiaoyong Xu; Xiaowen Zhai; Hong Xu; Zhiping Li Journal: Ann Transl Med Date: 2021-09