학술논문
In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation.
Document Type
Academic Journal
Author
Leonard AK; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN.; Furstenau D; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Department of Pediatrics, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.; Inam Z; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC.; Luckett C; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Chu R; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Demirci S; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Essawi K; Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia.; Gudmundsdottir B; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Hinds M; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; DiNicola J; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Li Q; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.; Eaton WA; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.; Cellmer T; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.; Wang X; Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.; Thein SL; Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.; Macari ER; bluebird bio, Inc, Somerville, MA.; VanNest S; bluebird bio, Inc, Somerville, MA.; Hsieh MM; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.; Bonner M; bluebird bio, Inc, Somerville, MA.; Pierciey FJ; bluebird bio, Inc, Somerville, MA.; Tisdale JF; Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
Source
Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
Subject
Language
English
Abstract
Abstract: Stable, mixed-donor-recipient chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease (SCD) is sufficient for phenotypic disease reversal, and results from differences in donor/recipient-red blood cell (RBC) survival. Understanding variability and predictors of RBC survival among patients with SCD before and after HSCT is critical for gene therapy research which seeks to generate sufficient corrected hemoglobin to reduce polymerization thereby overcoming the red cell pathology of SCD. This study used biotin labeling of RBCs to determine the lifespan of RBCs in patients with SCD compared with patients who have successfully undergone curative HSCT, participants with sickle cell trait (HbAS), and healthy (HbAA) donors. Twenty participants were included in the analysis (SCD pre-HSCT: N = 6, SCD post-HSCT: N = 5, HbAS: N = 6, and HbAA: N = 3). The average RBC lifespan was significantly shorter for participants with SCD pre-HSCT (64.1 days; range, 35-91) compared with those with SCD post-HSCT (113.4 days; range, 105-119), HbAS (126.0 days; range, 119-147), and HbAA (123.7 days; range, 91-147) (P<.001). RBC lifespan correlated with various hematologic parameters and strongly correlated with the average final fraction of sickled RBCs after deoxygenation (P<.001). No adverse events were attributable to the use of biotin and related procedures. Biotin labeling of RBCs is a safe and feasible methodology to evaluate RBC survival in patients with SCD before and after HSCT. Understanding differences in RBC survival may ultimately guide gene therapy protocols to determine hemoglobin composition required to reverse the SCD phenotype as it relates directly to RBC survival. This trial was registered at www.clinicaltrials.gov as #NCT04476277.
(Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)
(Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)