Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor

Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor

Background: Hematopoietic stem cell (HSC) gene therapy is potentially curative for sickle cell disease (SCD) provided that a sufficient quantity of long-term engrafting CD34+ HSCs can be safely collected and infused. In patients with SCD, peripheral blood (PB) mobilization with granulocyte colony st...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Blood 2019-11, Vol.134 (Supplement_1), p.1964-1964
Hauptverfasser: Leonard, Alexis, Uchida, Naoya, Stroncek, David F., Panch, Sandhya R., West, Kamille, Molloy, Eoghan George, Hughes, Tom, Hauffe, Sara, Taylor, Tiffani, Fitzhugh, Courtney D., Hankins, Jane S., Wilson, Megan, Sharma, Akshay, Tsai, Shengdar Q., Weiss, Mitchell J., Hsieh, Matthew, Tisdale, John F.
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1964
container_issue Supplement_1
container_start_page 1964
container_title Blood
container_volume 134
creator Leonard, Alexis
Uchida, Naoya
Stroncek, David F.
Panch, Sandhya R.
West, Kamille
Molloy, Eoghan George
Hughes, Tom
Hauffe, Sara
Taylor, Tiffani
Fitzhugh, Courtney D.
Hankins, Jane S.
Wilson, Megan
Sharma, Akshay
Tsai, Shengdar Q.
Weiss, Mitchell J.
Hsieh, Matthew
Tisdale, John F.
description Background: Hematopoietic stem cell (HSC) gene therapy is potentially curative for sickle cell disease (SCD) provided that a sufficient quantity of long-term engrafting CD34+ HSCs can be safely collected and infused. In patients with SCD, peripheral blood (PB) mobilization with granulocyte colony stimulating factor is contraindicated, and steady-state bone marrow (BM) harvesting is associated with suboptimal HSC quality and yield. Hence, agents that promote safe and effective peripheral HSC mobilization in SCD are required. Methods: This phase I multicenter study investigated the safety and efficacy of plerixafor mobilization (240 µg/kg) followed by apheresis, processing, and HSC enrichment in 15 adult subjects with SCD (NCT03226691). Hydroxyurea treatment was stopped at least two weeks prior to mobilization and all participants who were not receiving long-term transfusion therapy received prophylactic red blood cell exchange prior to plerixafor administration to achieve a target sickle Hb (HbS)
doi_str_mv 10.1182/blood-2019-126091
format Article
fullrecord <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2019_126091</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497118598815</els_id><sourcerecordid>S0006497118598815</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1371-9080fa64e17fe534800d71e6340f6f679dda4020da687ac670dd7a6037ec58e23</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EEqXwAez8A4Gxk9iJWEEoD6kSlUrXlrHH1OAmlR3x-HsSwprVbOZc3XsIOWdwwVjFL19C19mMA6szxgXU7IDMWMmrDIDDIZkBgMiKWrJjcpLSGwArcl7OSLvWDqluLV04543HtqcrjH6_xagDvRlj6brHHW0wBNp0IaDpfddS39KV7kcg0U_fb-nam_eA09-tT6gT0k3y7StdhSHxS7sunpIjp0PCs787J5u7xXPzkC2f7h-b62VmWC5ZVkMFTosCmXRY5kUFYCVDkRfghBOytlYXwzCrRSW1ERKslVpALtGUFfJ8TtiUa2KXUkSn9tHvdPxWDNQoTP0KU6MwNQkbmKuJwaHYh8eo0ujDoPVx2Kxs5_-hfwBN23OH</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Leonard, Alexis ; Uchida, Naoya ; Stroncek, David F. ; Panch, Sandhya R. ; West, Kamille ; Molloy, Eoghan George ; Hughes, Tom ; Hauffe, Sara ; Taylor, Tiffani ; Fitzhugh, Courtney D. ; Hankins, Jane S. ; Wilson, Megan ; Sharma, Akshay ; Tsai, Shengdar Q. ; Weiss, Mitchell J. ; Hsieh, Matthew ; Tisdale, John F.</creator><creatorcontrib>Leonard, Alexis ; Uchida, Naoya ; Stroncek, David F. ; Panch, Sandhya R. ; West, Kamille ; Molloy, Eoghan George ; Hughes, Tom ; Hauffe, Sara ; Taylor, Tiffani ; Fitzhugh, Courtney D. ; Hankins, Jane S. ; Wilson, Megan ; Sharma, Akshay ; Tsai, Shengdar Q. ; Weiss, Mitchell J. ; Hsieh, Matthew ; Tisdale, John F.</creatorcontrib><description>Background: Hematopoietic stem cell (HSC) gene therapy is potentially curative for sickle cell disease (SCD) provided that a sufficient quantity of long-term engrafting CD34+ HSCs can be safely collected and infused. In patients with SCD, peripheral blood (PB) mobilization with granulocyte colony stimulating factor is contraindicated, and steady-state bone marrow (BM) harvesting is associated with suboptimal HSC quality and yield. Hence, agents that promote safe and effective peripheral HSC mobilization in SCD are required. Methods: This phase I multicenter study investigated the safety and efficacy of plerixafor mobilization (240 µg/kg) followed by apheresis, processing, and HSC enrichment in 15 adult subjects with SCD (NCT03226691). Hydroxyurea treatment was stopped at least two weeks prior to mobilization and all participants who were not receiving long-term transfusion therapy received prophylactic red blood cell exchange prior to plerixafor administration to achieve a target sickle Hb (HbS) &lt;30%. The primary endpoint was efficient collection of PB HSCs (target 2.0x106 CD34+ cells/kg, minimum 1.5x106) after plerixafor mobilization without serious adverse events (SAEs). Collection products were assessed for total WBC, CD34+, CD3+, and CD19+ composition by flow cytometry. Spearman's correlation test was used to assess the relationship between baseline CD34/µL, total CD34+ cells/kg collected, and total blood volume processed. Findings: Fifteen participants with SCD (HbSS n=13, HbSC n=1, HbSβ+ n=1) who met inclusion criteria were enrolled at St. Jude Research Children's Hospital (n=3) or NIH (n=12) between July 2017 and February 2019. All participants except one successfully met the minimum target CD34+ cells/kg yield with 2 or fewer mobilization and apheresis procedures, with almost half the participants (n=7) achieving ≥5.0x106 CD34+ cells/kg. The total WBC count increased by an average of 3.2-fold over baseline (range 1.7-5.0) to an average peak WBC count of 26.5x103/µL (range 14.1-47.4), with counts returning to baseline within 1-2 days. Median total WBC, CD34+, CD19+, and CD3+ cells/kg in the final apheresis product after one (n=12) or two (n=3) collection procedures were 0.9 x109 WBC/kg (range 0.4-1.7), 4.5x106 CD34+ cells/kg (range 0.9-12.0), 3.4x108 CD19+ cells/kg (range 0.5-4.9), and 3.6x108 CD3+ cells/kg (range 1.7-7.3), respectively. There was a strong positive correlation between baseline CD34/µL and total CD34+ cells/kg (rs = 0.7776, 95% CI 0.446-0.9215, p = 0.001). Participants with the lowest pre-apheresis CD34 cell count generally underwent higher blood volume processing (rs = - 0.1443, 95% CI -0.6075 to 0.3921, p = 0.59) in an effort to achieve target yields. However, higher blood volume processing did not translate to higher total CD34+ cells/kg collection yields (rs = - 0.2104, 95% CI -0.6488 to 0.3328, p = 0.43). A median of 97% of positively selected CD34+ cells were CD34high (range 73.6-99.4%) compared to 1.3% CD34low (range 0.09-24.4%) phenotype suggesting enrichment for long-term engrafting HSCs. Seven grade III AEs (two non-pain and five pain related) and one grade IV AE (non-pain - hemolysis) occurred and each resolved with symptomatic treatment. Plerixafor mobilization was overall safe and in most cases generated CD34+ cell yields that were sufficient for both genetic modification and back-up allogeneic transplantation (median cell yield 4.2x106 CD34+ cells/kg). Interpretation: This first multi-institutional phase I study suggests the efficiency and safety of plerixafor mobilization and apheresis collection in 15 adult subjects with SCD. The primary endpoint to obtain a target of 2.0x106 CD34+ cells/kg from the PB was exceeded without SAEs. Importantly, immunophenotyping data suggest that for individuals with SCD, the plerixafor mobilized cell product is more enriched for long-term engrafting HSCs compared to CD34+ cells isolated from BM. Given the risks of general anesthesia and the low quality and yield of CD34+ cells harvested from the BM of individuals with SCD, plerixafor mobilization represents a safe and potentially superior alternative for HSC isolation. Hankins:Novartis: Research Funding; ASPHO: Honoraria; NHLBI: Research Funding; LYNKS Foundation: Research Funding; NHLBI: Honoraria; National Committee for Quality Assurance: Consultancy; Global Blood Therapeutics: Research Funding; Bluebird Bio: Consultancy. Sharma:Vertex Pharmaceuticals: Other: Study PI; Doris Duke Foundation: Research Funding. Weiss:GlaxoSmithKline: Consultancy; Rubius INC: Consultancy; Esperian: Consultancy; Beam Therapeutics: Consultancy; Cellarity INC: Consultancy.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2019-126091</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2019-11, Vol.134 (Supplement_1), p.1964-1964</ispartof><rights>2019 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids></links><search><creatorcontrib>Leonard, Alexis</creatorcontrib><creatorcontrib>Uchida, Naoya</creatorcontrib><creatorcontrib>Stroncek, David F.</creatorcontrib><creatorcontrib>Panch, Sandhya R.</creatorcontrib><creatorcontrib>West, Kamille</creatorcontrib><creatorcontrib>Molloy, Eoghan George</creatorcontrib><creatorcontrib>Hughes, Tom</creatorcontrib><creatorcontrib>Hauffe, Sara</creatorcontrib><creatorcontrib>Taylor, Tiffani</creatorcontrib><creatorcontrib>Fitzhugh, Courtney D.</creatorcontrib><creatorcontrib>Hankins, Jane S.</creatorcontrib><creatorcontrib>Wilson, Megan</creatorcontrib><creatorcontrib>Sharma, Akshay</creatorcontrib><creatorcontrib>Tsai, Shengdar Q.</creatorcontrib><creatorcontrib>Weiss, Mitchell J.</creatorcontrib><creatorcontrib>Hsieh, Matthew</creatorcontrib><creatorcontrib>Tisdale, John F.</creatorcontrib><title>Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor</title><title>Blood</title><description>Background: Hematopoietic stem cell (HSC) gene therapy is potentially curative for sickle cell disease (SCD) provided that a sufficient quantity of long-term engrafting CD34+ HSCs can be safely collected and infused. In patients with SCD, peripheral blood (PB) mobilization with granulocyte colony stimulating factor is contraindicated, and steady-state bone marrow (BM) harvesting is associated with suboptimal HSC quality and yield. Hence, agents that promote safe and effective peripheral HSC mobilization in SCD are required. Methods: This phase I multicenter study investigated the safety and efficacy of plerixafor mobilization (240 µg/kg) followed by apheresis, processing, and HSC enrichment in 15 adult subjects with SCD (NCT03226691). Hydroxyurea treatment was stopped at least two weeks prior to mobilization and all participants who were not receiving long-term transfusion therapy received prophylactic red blood cell exchange prior to plerixafor administration to achieve a target sickle Hb (HbS) &lt;30%. The primary endpoint was efficient collection of PB HSCs (target 2.0x106 CD34+ cells/kg, minimum 1.5x106) after plerixafor mobilization without serious adverse events (SAEs). Collection products were assessed for total WBC, CD34+, CD3+, and CD19+ composition by flow cytometry. Spearman's correlation test was used to assess the relationship between baseline CD34/µL, total CD34+ cells/kg collected, and total blood volume processed. Findings: Fifteen participants with SCD (HbSS n=13, HbSC n=1, HbSβ+ n=1) who met inclusion criteria were enrolled at St. Jude Research Children's Hospital (n=3) or NIH (n=12) between July 2017 and February 2019. All participants except one successfully met the minimum target CD34+ cells/kg yield with 2 or fewer mobilization and apheresis procedures, with almost half the participants (n=7) achieving ≥5.0x106 CD34+ cells/kg. The total WBC count increased by an average of 3.2-fold over baseline (range 1.7-5.0) to an average peak WBC count of 26.5x103/µL (range 14.1-47.4), with counts returning to baseline within 1-2 days. Median total WBC, CD34+, CD19+, and CD3+ cells/kg in the final apheresis product after one (n=12) or two (n=3) collection procedures were 0.9 x109 WBC/kg (range 0.4-1.7), 4.5x106 CD34+ cells/kg (range 0.9-12.0), 3.4x108 CD19+ cells/kg (range 0.5-4.9), and 3.6x108 CD3+ cells/kg (range 1.7-7.3), respectively. There was a strong positive correlation between baseline CD34/µL and total CD34+ cells/kg (rs = 0.7776, 95% CI 0.446-0.9215, p = 0.001). Participants with the lowest pre-apheresis CD34 cell count generally underwent higher blood volume processing (rs = - 0.1443, 95% CI -0.6075 to 0.3921, p = 0.59) in an effort to achieve target yields. However, higher blood volume processing did not translate to higher total CD34+ cells/kg collection yields (rs = - 0.2104, 95% CI -0.6488 to 0.3328, p = 0.43). A median of 97% of positively selected CD34+ cells were CD34high (range 73.6-99.4%) compared to 1.3% CD34low (range 0.09-24.4%) phenotype suggesting enrichment for long-term engrafting HSCs. Seven grade III AEs (two non-pain and five pain related) and one grade IV AE (non-pain - hemolysis) occurred and each resolved with symptomatic treatment. Plerixafor mobilization was overall safe and in most cases generated CD34+ cell yields that were sufficient for both genetic modification and back-up allogeneic transplantation (median cell yield 4.2x106 CD34+ cells/kg). Interpretation: This first multi-institutional phase I study suggests the efficiency and safety of plerixafor mobilization and apheresis collection in 15 adult subjects with SCD. The primary endpoint to obtain a target of 2.0x106 CD34+ cells/kg from the PB was exceeded without SAEs. Importantly, immunophenotyping data suggest that for individuals with SCD, the plerixafor mobilized cell product is more enriched for long-term engrafting HSCs compared to CD34+ cells isolated from BM. Given the risks of general anesthesia and the low quality and yield of CD34+ cells harvested from the BM of individuals with SCD, plerixafor mobilization represents a safe and potentially superior alternative for HSC isolation. Hankins:Novartis: Research Funding; ASPHO: Honoraria; NHLBI: Research Funding; LYNKS Foundation: Research Funding; NHLBI: Honoraria; National Committee for Quality Assurance: Consultancy; Global Blood Therapeutics: Research Funding; Bluebird Bio: Consultancy. Sharma:Vertex Pharmaceuticals: Other: Study PI; Doris Duke Foundation: Research Funding. Weiss:GlaxoSmithKline: Consultancy; Rubius INC: Consultancy; Esperian: Consultancy; Beam Therapeutics: Consultancy; Cellarity INC: Consultancy.</description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOwzAQRS0EEqXwAez8A4Gxk9iJWEEoD6kSlUrXlrHH1OAmlR3x-HsSwprVbOZc3XsIOWdwwVjFL19C19mMA6szxgXU7IDMWMmrDIDDIZkBgMiKWrJjcpLSGwArcl7OSLvWDqluLV04543HtqcrjH6_xagDvRlj6brHHW0wBNp0IaDpfddS39KV7kcg0U_fb-nam_eA09-tT6gT0k3y7StdhSHxS7sunpIjp0PCs787J5u7xXPzkC2f7h-b62VmWC5ZVkMFTosCmXRY5kUFYCVDkRfghBOytlYXwzCrRSW1ERKslVpALtGUFfJ8TtiUa2KXUkSn9tHvdPxWDNQoTP0KU6MwNQkbmKuJwaHYh8eo0ujDoPVx2Kxs5_-hfwBN23OH</recordid><startdate>20191113</startdate><enddate>20191113</enddate><creator>Leonard, Alexis</creator><creator>Uchida, Naoya</creator><creator>Stroncek, David F.</creator><creator>Panch, Sandhya R.</creator><creator>West, Kamille</creator><creator>Molloy, Eoghan George</creator><creator>Hughes, Tom</creator><creator>Hauffe, Sara</creator><creator>Taylor, Tiffani</creator><creator>Fitzhugh, Courtney D.</creator><creator>Hankins, Jane S.</creator><creator>Wilson, Megan</creator><creator>Sharma, Akshay</creator><creator>Tsai, Shengdar Q.</creator><creator>Weiss, Mitchell J.</creator><creator>Hsieh, Matthew</creator><creator>Tisdale, John F.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20191113</creationdate><title>Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor</title><author>Leonard, Alexis ; Uchida, Naoya ; Stroncek, David F. ; Panch, Sandhya R. ; West, Kamille ; Molloy, Eoghan George ; Hughes, Tom ; Hauffe, Sara ; Taylor, Tiffani ; Fitzhugh, Courtney D. ; Hankins, Jane S. ; Wilson, Megan ; Sharma, Akshay ; Tsai, Shengdar Q. ; Weiss, Mitchell J. ; Hsieh, Matthew ; Tisdale, John F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1371-9080fa64e17fe534800d71e6340f6f679dda4020da687ac670dd7a6037ec58e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leonard, Alexis</creatorcontrib><creatorcontrib>Uchida, Naoya</creatorcontrib><creatorcontrib>Stroncek, David F.</creatorcontrib><creatorcontrib>Panch, Sandhya R.</creatorcontrib><creatorcontrib>West, Kamille</creatorcontrib><creatorcontrib>Molloy, Eoghan George</creatorcontrib><creatorcontrib>Hughes, Tom</creatorcontrib><creatorcontrib>Hauffe, Sara</creatorcontrib><creatorcontrib>Taylor, Tiffani</creatorcontrib><creatorcontrib>Fitzhugh, Courtney D.</creatorcontrib><creatorcontrib>Hankins, Jane S.</creatorcontrib><creatorcontrib>Wilson, Megan</creatorcontrib><creatorcontrib>Sharma, Akshay</creatorcontrib><creatorcontrib>Tsai, Shengdar Q.</creatorcontrib><creatorcontrib>Weiss, Mitchell J.</creatorcontrib><creatorcontrib>Hsieh, Matthew</creatorcontrib><creatorcontrib>Tisdale, John F.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leonard, Alexis</au><au>Uchida, Naoya</au><au>Stroncek, David F.</au><au>Panch, Sandhya R.</au><au>West, Kamille</au><au>Molloy, Eoghan George</au><au>Hughes, Tom</au><au>Hauffe, Sara</au><au>Taylor, Tiffani</au><au>Fitzhugh, Courtney D.</au><au>Hankins, Jane S.</au><au>Wilson, Megan</au><au>Sharma, Akshay</au><au>Tsai, Shengdar Q.</au><au>Weiss, Mitchell J.</au><au>Hsieh, Matthew</au><au>Tisdale, John F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor</atitle><jtitle>Blood</jtitle><date>2019-11-13</date><risdate>2019</risdate><volume>134</volume><issue>Supplement_1</issue><spage>1964</spage><epage>1964</epage><pages>1964-1964</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Background: Hematopoietic stem cell (HSC) gene therapy is potentially curative for sickle cell disease (SCD) provided that a sufficient quantity of long-term engrafting CD34+ HSCs can be safely collected and infused. In patients with SCD, peripheral blood (PB) mobilization with granulocyte colony stimulating factor is contraindicated, and steady-state bone marrow (BM) harvesting is associated with suboptimal HSC quality and yield. Hence, agents that promote safe and effective peripheral HSC mobilization in SCD are required. Methods: This phase I multicenter study investigated the safety and efficacy of plerixafor mobilization (240 µg/kg) followed by apheresis, processing, and HSC enrichment in 15 adult subjects with SCD (NCT03226691). Hydroxyurea treatment was stopped at least two weeks prior to mobilization and all participants who were not receiving long-term transfusion therapy received prophylactic red blood cell exchange prior to plerixafor administration to achieve a target sickle Hb (HbS) &lt;30%. The primary endpoint was efficient collection of PB HSCs (target 2.0x106 CD34+ cells/kg, minimum 1.5x106) after plerixafor mobilization without serious adverse events (SAEs). Collection products were assessed for total WBC, CD34+, CD3+, and CD19+ composition by flow cytometry. Spearman's correlation test was used to assess the relationship between baseline CD34/µL, total CD34+ cells/kg collected, and total blood volume processed. Findings: Fifteen participants with SCD (HbSS n=13, HbSC n=1, HbSβ+ n=1) who met inclusion criteria were enrolled at St. Jude Research Children's Hospital (n=3) or NIH (n=12) between July 2017 and February 2019. All participants except one successfully met the minimum target CD34+ cells/kg yield with 2 or fewer mobilization and apheresis procedures, with almost half the participants (n=7) achieving ≥5.0x106 CD34+ cells/kg. The total WBC count increased by an average of 3.2-fold over baseline (range 1.7-5.0) to an average peak WBC count of 26.5x103/µL (range 14.1-47.4), with counts returning to baseline within 1-2 days. Median total WBC, CD34+, CD19+, and CD3+ cells/kg in the final apheresis product after one (n=12) or two (n=3) collection procedures were 0.9 x109 WBC/kg (range 0.4-1.7), 4.5x106 CD34+ cells/kg (range 0.9-12.0), 3.4x108 CD19+ cells/kg (range 0.5-4.9), and 3.6x108 CD3+ cells/kg (range 1.7-7.3), respectively. There was a strong positive correlation between baseline CD34/µL and total CD34+ cells/kg (rs = 0.7776, 95% CI 0.446-0.9215, p = 0.001). Participants with the lowest pre-apheresis CD34 cell count generally underwent higher blood volume processing (rs = - 0.1443, 95% CI -0.6075 to 0.3921, p = 0.59) in an effort to achieve target yields. However, higher blood volume processing did not translate to higher total CD34+ cells/kg collection yields (rs = - 0.2104, 95% CI -0.6488 to 0.3328, p = 0.43). A median of 97% of positively selected CD34+ cells were CD34high (range 73.6-99.4%) compared to 1.3% CD34low (range 0.09-24.4%) phenotype suggesting enrichment for long-term engrafting HSCs. Seven grade III AEs (two non-pain and five pain related) and one grade IV AE (non-pain - hemolysis) occurred and each resolved with symptomatic treatment. Plerixafor mobilization was overall safe and in most cases generated CD34+ cell yields that were sufficient for both genetic modification and back-up allogeneic transplantation (median cell yield 4.2x106 CD34+ cells/kg). Interpretation: This first multi-institutional phase I study suggests the efficiency and safety of plerixafor mobilization and apheresis collection in 15 adult subjects with SCD. The primary endpoint to obtain a target of 2.0x106 CD34+ cells/kg from the PB was exceeded without SAEs. Importantly, immunophenotyping data suggest that for individuals with SCD, the plerixafor mobilized cell product is more enriched for long-term engrafting HSCs compared to CD34+ cells isolated from BM. Given the risks of general anesthesia and the low quality and yield of CD34+ cells harvested from the BM of individuals with SCD, plerixafor mobilization represents a safe and potentially superior alternative for HSC isolation. Hankins:Novartis: Research Funding; ASPHO: Honoraria; NHLBI: Research Funding; LYNKS Foundation: Research Funding; NHLBI: Honoraria; National Committee for Quality Assurance: Consultancy; Global Blood Therapeutics: Research Funding; Bluebird Bio: Consultancy. Sharma:Vertex Pharmaceuticals: Other: Study PI; Doris Duke Foundation: Research Funding. Weiss:GlaxoSmithKline: Consultancy; Rubius INC: Consultancy; Esperian: Consultancy; Beam Therapeutics: Consultancy; Cellarity INC: Consultancy.</abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2019-126091</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0006-4971
ispartof Blood, 2019-11, Vol.134 (Supplement_1), p.1964-1964
issn 0006-4971
1528-0020
language eng
recordid cdi_crossref_primary_10_1182_blood_2019_126091
source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
title Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T20%3A56%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Safe%20and%20Efficient%20Peripheral%20Blood%20Stem%20Cell%20Collection%20in%20Patients%20with%20Sickle%20Cell%20Disease%20Using%20Plerixafor&rft.jtitle=Blood&rft.au=Leonard,%20Alexis&rft.date=2019-11-13&rft.volume=134&rft.issue=Supplement_1&rft.spage=1964&rft.epage=1964&rft.pages=1964-1964&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2019-126091&rft_dat=%3Celsevier_cross%3ES0006497118598815%3C/elsevier_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_els_id=S0006497118598815&rfr_iscdi=true