In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation
•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 inform hemoglobin composition thresholds required to reverse the phenotype after gene therapy. [Display omitted] Stable, mixe...
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| Veröffentlicht in: | Blood advances 2024-04, Vol.8 (7), p.1806-1816 |
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| creator | Leonard, Alexis K. Furstenau, Dana Inam, Zaina Luckett, Christina Chu, Rebecca Demirci, Selami Essawi, Khaled Gudmundsdottir, Bjorg Hinds, Malikiya DiNicola, Julia Li, Quan Eaton, William A. Cellmer, Troy Wang, Xunde Thein, Swee Lay Macari, Elizabeth R. VanNest, Sara Hsieh, Matthew M. Bonner, Melissa Pierciey, Francis J. Tisdale, John F. |
| description | •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 inform hemoglobin composition thresholds required to reverse the phenotype after gene therapy.
[Display omitted]
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 |
| doi_str_mv | 10.1182/bloodadvances.2023011397 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11006808</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2473952924000193</els_id><sourcerecordid>2928996831</sourcerecordid><originalsourceid>FETCH-LOGICAL-c480t-52b803a864c9af4555dd3822cc6e35104005e554a62697568ddadd4f962902773</originalsourceid><addsrcrecordid>eNqFUcluHCEQRZGj2HL8CxHHXMZhaWg4RfEoiyVLlqzkjBiozmB3QweYjnLLpwdr7Il98qkovaWoeghhSs4pVezDZkzJW7_Y6KCcM8I4oZTr_hU6YV3PV1rw_ujwZvoYnZVySwihveRCszfomCuqaK-6E_T3MuIlLAlPYMsuwwSx4jTgm4s1bn2D7IhDxLOtoUEF_w51i0twdyNgB-OIfShNCngDQ8qAU8Z2qJDxFiZb05wC1OBwqTDt-TXbWObRxtosU3yLXg92LHD2UE_Rjy-fv6-_ra6uv16uP12tXKdIXQm2UYRbJTun7dAJIbznijHnJHBBSUeIACE6K5nUvZDKtxP5btCSacL6np-ij3vfebeZwLu2TLajmXOYbP5jkg3mORLD1vxMi6GUEKmIag7vHxxy-rWDUs0Uyv1KNkLaFcM0U1pLxWmjqj3V5VRKhuEwhxJzH6J5FqL5H2KTvnv6z4PwMbJGuNgToF1rCZBNcS0aBz5kcNX4FF6e8g9yUrXn</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2928996831</pqid></control><display><type>article</type><title>In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Leonard, Alexis K. ; Furstenau, Dana ; Inam, Zaina ; Luckett, Christina ; Chu, Rebecca ; Demirci, Selami ; Essawi, Khaled ; Gudmundsdottir, Bjorg ; Hinds, Malikiya ; DiNicola, Julia ; Li, Quan ; Eaton, William A. ; Cellmer, Troy ; Wang, Xunde ; Thein, Swee Lay ; Macari, Elizabeth R. ; VanNest, Sara ; Hsieh, Matthew M. ; Bonner, Melissa ; Pierciey, Francis J. ; Tisdale, John F.</creator><creatorcontrib>Leonard, Alexis K. ; Furstenau, Dana ; Inam, Zaina ; Luckett, Christina ; Chu, Rebecca ; Demirci, Selami ; Essawi, Khaled ; Gudmundsdottir, Bjorg ; Hinds, Malikiya ; DiNicola, Julia ; Li, Quan ; Eaton, William A. ; Cellmer, Troy ; Wang, Xunde ; Thein, Swee Lay ; Macari, Elizabeth R. ; VanNest, Sara ; Hsieh, Matthew M. ; Bonner, Melissa ; Pierciey, Francis J. ; Tisdale, John F.</creatorcontrib><description>•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 inform hemoglobin composition thresholds required to reverse the phenotype after gene therapy.
[Display omitted]
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.</description><identifier>ISSN: 2473-9529</identifier><identifier>ISSN: 2473-9537</identifier><identifier>EISSN: 2473-9537</identifier><identifier>DOI: 10.1182/bloodadvances.2023011397</identifier><identifier>PMID: 38181784</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anemia, Sickle Cell - pathology ; Biotin ; Clinical Trials and Observations ; Erythrocytes - pathology ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation - methods ; Hemoglobins ; Humans</subject><ispartof>Blood advances, 2024-04, Vol.8 (7), p.1806-1816</ispartof><rights>2024 The American Society of Hematology</rights><rights>Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.</rights><rights>Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. 2024 The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-52b803a864c9af4555dd3822cc6e35104005e554a62697568ddadd4f962902773</citedby><cites>FETCH-LOGICAL-c480t-52b803a864c9af4555dd3822cc6e35104005e554a62697568ddadd4f962902773</cites><orcidid>0000-0002-9244-5407 ; 0000-0002-9835-6501 ; 0000-0003-0022-4138 ; 0000-0002-6174-1609 ; 0009-0003-9556-5249</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006808/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006808/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38181784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leonard, Alexis K.</creatorcontrib><creatorcontrib>Furstenau, Dana</creatorcontrib><creatorcontrib>Inam, Zaina</creatorcontrib><creatorcontrib>Luckett, Christina</creatorcontrib><creatorcontrib>Chu, Rebecca</creatorcontrib><creatorcontrib>Demirci, Selami</creatorcontrib><creatorcontrib>Essawi, Khaled</creatorcontrib><creatorcontrib>Gudmundsdottir, Bjorg</creatorcontrib><creatorcontrib>Hinds, Malikiya</creatorcontrib><creatorcontrib>DiNicola, Julia</creatorcontrib><creatorcontrib>Li, Quan</creatorcontrib><creatorcontrib>Eaton, William A.</creatorcontrib><creatorcontrib>Cellmer, Troy</creatorcontrib><creatorcontrib>Wang, Xunde</creatorcontrib><creatorcontrib>Thein, Swee Lay</creatorcontrib><creatorcontrib>Macari, Elizabeth R.</creatorcontrib><creatorcontrib>VanNest, Sara</creatorcontrib><creatorcontrib>Hsieh, Matthew M.</creatorcontrib><creatorcontrib>Bonner, Melissa</creatorcontrib><creatorcontrib>Pierciey, Francis J.</creatorcontrib><creatorcontrib>Tisdale, John F.</creatorcontrib><title>In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation</title><title>Blood advances</title><addtitle>Blood Adv</addtitle><description>•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 inform hemoglobin composition thresholds required to reverse the phenotype after gene therapy.
[Display omitted]
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.</description><subject>Anemia, Sickle Cell - pathology</subject><subject>Biotin</subject><subject>Clinical Trials and Observations</subject><subject>Erythrocytes - pathology</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hemoglobins</subject><subject>Humans</subject><issn>2473-9529</issn><issn>2473-9537</issn><issn>2473-9537</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUcluHCEQRZGj2HL8CxHHXMZhaWg4RfEoiyVLlqzkjBiozmB3QweYjnLLpwdr7Il98qkovaWoeghhSs4pVezDZkzJW7_Y6KCcM8I4oZTr_hU6YV3PV1rw_ujwZvoYnZVySwihveRCszfomCuqaK-6E_T3MuIlLAlPYMsuwwSx4jTgm4s1bn2D7IhDxLOtoUEF_w51i0twdyNgB-OIfShNCngDQ8qAU8Z2qJDxFiZb05wC1OBwqTDt-TXbWObRxtosU3yLXg92LHD2UE_Rjy-fv6-_ra6uv16uP12tXKdIXQm2UYRbJTun7dAJIbznijHnJHBBSUeIACE6K5nUvZDKtxP5btCSacL6np-ij3vfebeZwLu2TLajmXOYbP5jkg3mORLD1vxMi6GUEKmIag7vHxxy-rWDUs0Uyv1KNkLaFcM0U1pLxWmjqj3V5VRKhuEwhxJzH6J5FqL5H2KTvnv6z4PwMbJGuNgToF1rCZBNcS0aBz5kcNX4FF6e8g9yUrXn</recordid><startdate>20240409</startdate><enddate>20240409</enddate><creator>Leonard, Alexis K.</creator><creator>Furstenau, Dana</creator><creator>Inam, Zaina</creator><creator>Luckett, Christina</creator><creator>Chu, Rebecca</creator><creator>Demirci, Selami</creator><creator>Essawi, Khaled</creator><creator>Gudmundsdottir, Bjorg</creator><creator>Hinds, Malikiya</creator><creator>DiNicola, Julia</creator><creator>Li, Quan</creator><creator>Eaton, William A.</creator><creator>Cellmer, Troy</creator><creator>Wang, Xunde</creator><creator>Thein, Swee Lay</creator><creator>Macari, Elizabeth R.</creator><creator>VanNest, Sara</creator><creator>Hsieh, Matthew M.</creator><creator>Bonner, Melissa</creator><creator>Pierciey, Francis J.</creator><creator>Tisdale, John F.</creator><general>Elsevier Inc</general><general>The American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9244-5407</orcidid><orcidid>https://orcid.org/0000-0002-9835-6501</orcidid><orcidid>https://orcid.org/0000-0003-0022-4138</orcidid><orcidid>https://orcid.org/0000-0002-6174-1609</orcidid><orcidid>https://orcid.org/0009-0003-9556-5249</orcidid></search><sort><creationdate>20240409</creationdate><title>In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation</title><author>Leonard, Alexis K. ; 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[Display omitted]
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38181784</pmid><doi>10.1182/bloodadvances.2023011397</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-9244-5407</orcidid><orcidid>https://orcid.org/0000-0002-9835-6501</orcidid><orcidid>https://orcid.org/0000-0003-0022-4138</orcidid><orcidid>https://orcid.org/0000-0002-6174-1609</orcidid><orcidid>https://orcid.org/0009-0003-9556-5249</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Anemia, Sickle Cell - pathology Biotin Clinical Trials and Observations Erythrocytes - pathology Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - methods Hemoglobins Humans |
| title | In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation |
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