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Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study
Stroke is a major cause of death and long‐term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052613/ https://www.ncbi.nlm.nih.gov/pubmed/29752869 http://dx.doi.org/10.1002/sctm.18-0008 |
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author | Laskowitz, Daniel T. Bennett, Ellen R. Durham, Rebecca J. Volpi, John J. Wiese, Jonathan R. Frankel, Michael Shpall, Elizabeth Wilson, Jeffry M. Troy, Jesse Kurtzberg, Joanne |
author_facet | Laskowitz, Daniel T. Bennett, Ellen R. Durham, Rebecca J. Volpi, John J. Wiese, Jonathan R. Frankel, Michael Shpall, Elizabeth Wilson, Jeffry M. Troy, Jesse Kurtzberg, Joanne |
author_sort | Laskowitz, Daniel T. |
collection | PubMed |
description | Stroke is a major cause of death and long‐term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open‐label trial to assess the safety and feasibility of a single IV infusion of non‐human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3–9 days post‐stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well‐tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post‐treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non‐HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo‐controlled phase 2 study. stem cells translational medicine 2018;7:521–529 |
format | Online Article Text |
id | pubmed-6052613 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60526132018-07-23 Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study Laskowitz, Daniel T. Bennett, Ellen R. Durham, Rebecca J. Volpi, John J. Wiese, Jonathan R. Frankel, Michael Shpall, Elizabeth Wilson, Jeffry M. Troy, Jesse Kurtzberg, Joanne Stem Cells Transl Med Translational Research Articles and Reviews Stroke is a major cause of death and long‐term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open‐label trial to assess the safety and feasibility of a single IV infusion of non‐human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3–9 days post‐stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well‐tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post‐treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non‐HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo‐controlled phase 2 study. stem cells translational medicine 2018;7:521–529 John Wiley and Sons Inc. 2018-05-12 /pmc/articles/PMC6052613/ /pubmed/29752869 http://dx.doi.org/10.1002/sctm.18-0008 Text en © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Translational Research Articles and Reviews Laskowitz, Daniel T. Bennett, Ellen R. Durham, Rebecca J. Volpi, John J. Wiese, Jonathan R. Frankel, Michael Shpall, Elizabeth Wilson, Jeffry M. Troy, Jesse Kurtzberg, Joanne Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study |
title | Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study |
title_full | Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study |
title_fullStr | Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study |
title_full_unstemmed | Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study |
title_short | Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study |
title_sort | allogeneic umbilical cord blood infusion for adults with ischemic stroke: clinical outcomes from a phase i safety study |
topic | Translational Research Articles and Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052613/ https://www.ncbi.nlm.nih.gov/pubmed/29752869 http://dx.doi.org/10.1002/sctm.18-0008 |
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