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Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial
PURPOSE: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. EXPERIMENTAL DESIGN: An investigator-initiated, randomized,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365378/ https://www.ncbi.nlm.nih.gov/pubmed/35486613 http://dx.doi.org/10.1158/1078-0432.CCR-21-4520 |
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author | Lynggaard, Charlotte Duch Grønhøj, Christian Jensen, Siri B. Christensen, Robin Specht, Lena Andersen, Elo Andersen, Tobias T. Ciochon, Urszula M. Rathje, Gulla S. Hansen, Adam E. Stampe, Helene Fischer-Nielsen, Anne von Buchwald, Christian |
author_facet | Lynggaard, Charlotte Duch Grønhøj, Christian Jensen, Siri B. Christensen, Robin Specht, Lena Andersen, Elo Andersen, Tobias T. Ciochon, Urszula M. Rathje, Gulla S. Hansen, Adam E. Stampe, Helene Fischer-Nielsen, Anne von Buchwald, Christian |
author_sort | Lynggaard, Charlotte Duch |
collection | PubMed |
description | PURPOSE: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. EXPERIMENTAL DESIGN: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm(3) injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models. RESULTS: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00–0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [−10.1 (−18.1 to −2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC. CONCLUSIONS: Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted. |
format | Online Article Text |
id | pubmed-9365378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-93653782023-01-05 Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial Lynggaard, Charlotte Duch Grønhøj, Christian Jensen, Siri B. Christensen, Robin Specht, Lena Andersen, Elo Andersen, Tobias T. Ciochon, Urszula M. Rathje, Gulla S. Hansen, Adam E. Stampe, Helene Fischer-Nielsen, Anne von Buchwald, Christian Clin Cancer Res Translational Cancer Mechanisms and Therapy PURPOSE: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. EXPERIMENTAL DESIGN: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm(3) injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models. RESULTS: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00–0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [−10.1 (−18.1 to −2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC. CONCLUSIONS: Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted. American Association for Cancer Research 2022-07-01 2022-04-29 /pmc/articles/PMC9365378/ /pubmed/35486613 http://dx.doi.org/10.1158/1078-0432.CCR-21-4520 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Translational Cancer Mechanisms and Therapy Lynggaard, Charlotte Duch Grønhøj, Christian Jensen, Siri B. Christensen, Robin Specht, Lena Andersen, Elo Andersen, Tobias T. Ciochon, Urszula M. Rathje, Gulla S. Hansen, Adam E. Stampe, Helene Fischer-Nielsen, Anne von Buchwald, Christian Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial |
title | Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial |
title_full | Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial |
title_fullStr | Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial |
title_full_unstemmed | Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial |
title_short | Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial |
title_sort | long-term safety of treatment with autologous mesenchymal stem cells in patients with radiation-induced xerostomia: primary results of the mesrix phase i/ii randomized trial |
topic | Translational Cancer Mechanisms and Therapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365378/ https://www.ncbi.nlm.nih.gov/pubmed/35486613 http://dx.doi.org/10.1158/1078-0432.CCR-21-4520 |
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