Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation

• Published in: Current controlled trials in cardiovascular medicine 2012-11, Vol.13 (1), p.211-211, Article 211
• Main Authors: Dillmann, Johannes, Popp, Felix C, Fillenberg, Barbara, Zeman, Florian, Eggenhofer, Elke, Farkas, Stefan, Scherer, Marcus N, Koller, Michael, Geissler, Edward K, Deans, Robert, Ladenheim, Deborah, Loss, Martin, Schlitt, Hans J, Dahlke, Marc H
• Format: Article
• Language: English
• Subjects: Adherent adult stem cells; Adult; Analysis; Chi-Square Distribution; Decision Support Techniques; Disease-Free Survival; Drug dosages; Drug therapy; Extubation; Female; Graft Rejection - etiology; Humans; Immunology; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Immunotherapy; Kaplan-Meier Estimate; Liver; Liver Transplantation - adverse effects; Liver Transplantation - immunology; Liver Transplantation - mortality; Lung Diseases - etiology; Male; Mesenchymal stem cells; Middle Aged; Multipotent adult progenitor cells; Patients; Phase I trial; Postoperative Complications - etiology; Postoperative Complications - immunology; Postoperative Complications - mortality; Predictive Value of Tests; Reproducibility of Results; Respiratory distress syndrome; Retrospective Studies; Risk Assessment; Risk Factors; Scoring adverse events; Severity of Illness Index; Solid organ transplantation; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - mortality; Stem cells; Time Factors; Transplantation; Treatment Outcome; Veins & arteries; Ventilators; Weaning; Young Adult
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/1745-6215-13-211

Cellular therapy after organ transplantation is emerging as an intriguing strategy to achieve dose reduction of classical immunosuppressive pharmacotherapy. Here, we introduce a new scoring system to assess treatment-emergent adverse events (TEAEs) of adherent stem cell therapies in the clinical setting of allogeneic liver transplantation (for example, the MiSOT-I trial Eudract CT: 2009-017795-25). The score consists of three independent modalities (set of parameters) that focus on clinically relevant events early after intravenous or intraportal stem cell infusion: pulmonary toxicity, intraportal-infusional toxicity and systemic toxicity. For each modality, values between 0 (no TEAE) and 3 (severe TEAE) were defined. The score was validated retrospectively on a cohort of n=187 recipients of liver allografts not receiving investigational cell therapy between July 2004 and December 2010. These patients represent a control population for further trials. Score values were calculated for days 1, 4, and 10 after liver transplantation. Grade 3 events were most commonly related to the pulmonary system (3.5% of study cohort on day 4). Almost no systemic-related TEAEs were observed during the study period. The relative frequency of grade 3 events never exceeded 5% over all modalities and time points. A subgroup analysis for grade 3 patients provided no descriptors associated with severe TEAEs. The MiSOT-I score provides an assessment tool to score specific adverse events that may occur after adherent stem cell therapy in the clinical setting of organ transplantation and is thus a helpful tool to conduct a safety study.