Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience
Abstract Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compa...
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| Veröffentlicht in: | Stem cells translational medicine 2022-04, Vol.11 (4), p.343-355 |
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| creator | Macías-Sánchez, María del Mar Morata-Tarifa, Cynthia Cuende, Natividad Cardesa-Gil, Ana Cuesta-Casas, María Ángeles Pascual-Cascon, María Jesús Pascual, Antonia Martín-Calvo, Carmen Jurado, Manuel Perez-Simón, José Antonio Espigado, Ildefonso Garzón López, Sebastián Carmona Sánchez, Gloria Mata-Alcázar-Caballero, Rosario Sánchez-Pernaute, Rosario |
| description | Abstract
Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.
Graphical Abstract
Graphical Abstract |
| doi_str_mv | 10.1093/stcltm/szac003 |
| format | Article |
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Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.
Graphical Abstract
Graphical Abstract</description><identifier>ISSN: 2157-6564</identifier><identifier>EISSN: 2157-6580</identifier><identifier>DOI: 10.1093/stcltm/szac003</identifier><identifier>PMID: 35348788</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Acute Disease ; Adolescent ; Adult ; Aged ; Child ; Compassionate Use Trials - adverse effects ; Female ; Graft vs Host Disease - etiology ; Graft vs Host Disease - therapy ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation - methods ; Human Clinical ; Humans ; Male ; Mesenchymal Stem Cell Transplantation - adverse effects ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stem Cells ; Middle Aged ; Steroids - therapeutic use ; Young Adult</subject><ispartof>Stem cells translational medicine, 2022-04, Vol.11 (4), p.343-355</ispartof><rights>The Author(s) 2022. Published by Oxford University Press. 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-519536e83329268e5346ce1e6d158cf56211d99afd9cc1958b4daac08f5f0c313</citedby><cites>FETCH-LOGICAL-c469t-519536e83329268e5346ce1e6d158cf56211d99afd9cc1958b4daac08f5f0c313</cites><orcidid>0000-0003-1144-9025 ; 0000-0002-4291-5116</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/PMC9052408/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052408/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,1598,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35348788$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Macías-Sánchez, María del Mar</creatorcontrib><creatorcontrib>Morata-Tarifa, Cynthia</creatorcontrib><creatorcontrib>Cuende, Natividad</creatorcontrib><creatorcontrib>Cardesa-Gil, Ana</creatorcontrib><creatorcontrib>Cuesta-Casas, María Ángeles</creatorcontrib><creatorcontrib>Pascual-Cascon, María Jesús</creatorcontrib><creatorcontrib>Pascual, Antonia</creatorcontrib><creatorcontrib>Martín-Calvo, Carmen</creatorcontrib><creatorcontrib>Jurado, Manuel</creatorcontrib><creatorcontrib>Perez-Simón, José Antonio</creatorcontrib><creatorcontrib>Espigado, Ildefonso</creatorcontrib><creatorcontrib>Garzón López, Sebastián</creatorcontrib><creatorcontrib>Carmona Sánchez, Gloria</creatorcontrib><creatorcontrib>Mata-Alcázar-Caballero, Rosario</creatorcontrib><creatorcontrib>Sánchez-Pernaute, Rosario</creatorcontrib><title>Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience</title><title>Stem cells translational medicine</title><addtitle>Stem Cells Transl Med</addtitle><description>Abstract
Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.
Graphical Abstract
Graphical Abstract</description><subject>Acute Disease</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Child</subject><subject>Compassionate Use Trials - adverse effects</subject><subject>Female</subject><subject>Graft vs Host Disease - etiology</subject><subject>Graft vs Host Disease - therapy</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Human Clinical</subject><subject>Humans</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation - adverse effects</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stem Cells</subject><subject>Middle Aged</subject><subject>Steroids - therapeutic use</subject><subject>Young Adult</subject><issn>2157-6564</issn><issn>2157-6580</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EolXplSPyEQ5p_SdxbQ5Iq7S0SK2QoOVquc6ka5TEweMgyqfgI-PVLis44ctYmp_fPM8j5CVnJ5wZeYrZD3k8xZ_OMyafkEPBm7NKNZo93d9VfUCOEb-ycpRRRrDn5EA2stZnWh-SXzeAMPn14-gG-jmnuKktDAPSPiZ6m8DlMD2UFqQYuuoTYMDspkxXfslA3dTRdp3iFDy9TK7P9AskXJBeRcz0PCA4hLd0RW-WIQcPU9GhbRxnhxji5IrEHQK9-DFDCsUIvCDPejcgHO_qEbl7f3HbXlXXHy8_tKvrytfK5KrhppEKtJTCCKWhfEh54KA63mjfN0pw3hnj-s54X1h9X3eurEn3Tc-85PKIvNvqzsv9CN3GWXKDnVMYXXq00QX7b2cKa_sQv1vDGlEzXQRe7wRS_LYAZjsG9GVzboK4oBWqrk0tmBIFPdmiPkXEBP1-DGd2k6TdJml3SZYHr_42t8f_5FaAN1sgLvP_xH4D4BquAg</recordid><startdate>20220429</startdate><enddate>20220429</enddate><creator>Macías-Sánchez, María del Mar</creator><creator>Morata-Tarifa, Cynthia</creator><creator>Cuende, Natividad</creator><creator>Cardesa-Gil, Ana</creator><creator>Cuesta-Casas, María Ángeles</creator><creator>Pascual-Cascon, María Jesús</creator><creator>Pascual, Antonia</creator><creator>Martín-Calvo, Carmen</creator><creator>Jurado, Manuel</creator><creator>Perez-Simón, José Antonio</creator><creator>Espigado, Ildefonso</creator><creator>Garzón López, Sebastián</creator><creator>Carmona Sánchez, Gloria</creator><creator>Mata-Alcázar-Caballero, Rosario</creator><creator>Sánchez-Pernaute, Rosario</creator><general>Oxford University Press</general><scope>TOX</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/0000-0003-1144-9025</orcidid><orcidid>https://orcid.org/0000-0002-4291-5116</orcidid></search><sort><creationdate>20220429</creationdate><title>Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience</title><author>Macías-Sánchez, María del Mar ; Morata-Tarifa, Cynthia ; Cuende, Natividad ; Cardesa-Gil, Ana ; Cuesta-Casas, María Ángeles ; Pascual-Cascon, María Jesús ; Pascual, Antonia ; Martín-Calvo, Carmen ; Jurado, Manuel ; Perez-Simón, José Antonio ; Espigado, Ildefonso ; Garzón López, Sebastián ; Carmona Sánchez, Gloria ; Mata-Alcázar-Caballero, Rosario ; Sánchez-Pernaute, Rosario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-519536e83329268e5346ce1e6d158cf56211d99afd9cc1958b4daac08f5f0c313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acute Disease</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Child</topic><topic>Compassionate Use Trials - adverse effects</topic><topic>Female</topic><topic>Graft vs Host Disease - etiology</topic><topic>Graft vs Host Disease - therapy</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Human Clinical</topic><topic>Humans</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation - adverse effects</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stem Cells</topic><topic>Middle Aged</topic><topic>Steroids - therapeutic use</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Macías-Sánchez, María del Mar</creatorcontrib><creatorcontrib>Morata-Tarifa, Cynthia</creatorcontrib><creatorcontrib>Cuende, Natividad</creatorcontrib><creatorcontrib>Cardesa-Gil, Ana</creatorcontrib><creatorcontrib>Cuesta-Casas, María Ángeles</creatorcontrib><creatorcontrib>Pascual-Cascon, María Jesús</creatorcontrib><creatorcontrib>Pascual, Antonia</creatorcontrib><creatorcontrib>Martín-Calvo, Carmen</creatorcontrib><creatorcontrib>Jurado, Manuel</creatorcontrib><creatorcontrib>Perez-Simón, José Antonio</creatorcontrib><creatorcontrib>Espigado, Ildefonso</creatorcontrib><creatorcontrib>Garzón López, Sebastián</creatorcontrib><creatorcontrib>Carmona Sánchez, Gloria</creatorcontrib><creatorcontrib>Mata-Alcázar-Caballero, Rosario</creatorcontrib><creatorcontrib>Sánchez-Pernaute, Rosario</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cells translational medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Macías-Sánchez, María del Mar</au><au>Morata-Tarifa, Cynthia</au><au>Cuende, Natividad</au><au>Cardesa-Gil, Ana</au><au>Cuesta-Casas, María Ángeles</au><au>Pascual-Cascon, María Jesús</au><au>Pascual, Antonia</au><au>Martín-Calvo, Carmen</au><au>Jurado, Manuel</au><au>Perez-Simón, José Antonio</au><au>Espigado, Ildefonso</au><au>Garzón López, Sebastián</au><au>Carmona Sánchez, Gloria</au><au>Mata-Alcázar-Caballero, Rosario</au><au>Sánchez-Pernaute, Rosario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience</atitle><jtitle>Stem cells translational medicine</jtitle><addtitle>Stem Cells Transl Med</addtitle><date>2022-04-29</date><risdate>2022</risdate><volume>11</volume><issue>4</issue><spage>343</spage><epage>355</epage><pages>343-355</pages><issn>2157-6564</issn><eissn>2157-6580</eissn><abstract>Abstract
Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.
Graphical Abstract
Graphical Abstract</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>35348788</pmid><doi>10.1093/stcltm/szac003</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-1144-9025</orcidid><orcidid>https://orcid.org/0000-0002-4291-5116</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acute Disease Adolescent Adult Aged Child Compassionate Use Trials - adverse effects Female Graft vs Host Disease - etiology Graft vs Host Disease - therapy Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - methods Human Clinical Humans Male Mesenchymal Stem Cell Transplantation - adverse effects Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stem Cells Middle Aged Steroids - therapeutic use Young Adult |
| title | Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience |
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