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Open Access Research

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

Johannes Dillmann1, Felix C Popp1, Barbara Fillenberg1, Florian Zeman2, Elke Eggenhofer1, Stefan Farkas1, Marcus N Scherer1, Michael Koller2, Edward K Geissler1, Robert Deans3, Deborah Ladenheim3, Martin Loss1, Hans J Schlitt1 and Marc H Dahlke1*

Author Affiliations

1 Department of Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany

2 Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany

3 Athersys Inc., Cleveland, OH, USA

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Trials 2012, 13:211  doi:10.1186/1745-6215-13-211

Published: 15 November 2012

Abstract

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Keywords:
Adherent adult stem cells; Mesenchymal stem cells; Multipotent adult progenitor cells; Solid organ transplantation; Immunotherapy; Scoring adverse events; Phase I trial