title: Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany. marc.dahlke@ukr.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Dillmann
authors.forename: Felix C
authors.initials: FC
authors.lastname: Popp
authors.forename: Barbara
authors.initials: B
authors.lastname: Fillenberg
authors.forename: Florian
authors.initials: F
authors.lastname: Zeman
authors.forename: Elke
authors.initials: E
authors.lastname: Eggenhofer
authors.forename: Stefan
authors.initials: S
authors.lastname: Farkas
authors.forename: Marcus N
authors.initials: MN
authors.lastname: Scherer
authors.forename: Michael
authors.initials: M
authors.lastname: Koller
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Robert
authors.initials: R
authors.lastname: Deans
authors.forename: Deborah
authors.initials: D
authors.lastname: Ladenheim
authors.forename: Martin
authors.initials: M
authors.lastname: Loss
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: Marc H
authors.initials: MH
authors.lastname: Dahlke
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D008171:Lung Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents