Granulocyte colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: a multicenter randomized trial (GRAFT-Trial)
Zusammenfassung der Projektergebnisse
The GRAFT trial was initiated when small, single-centre interventional trials provided intriguing and promising results for G-CSF. International guidelines for the treatment of patients with end-stage liver disease (e.g. APASL, EASL) discussed G-CSF as a therapy for ACLF but requested confirmatory data. Therefore, this project aimed at changing treatment strategies by implementing G-CSF as a novel therapy based on robust data from a well designed, first multi-center interventional trial. It was believed that G-CSF modulates the systemic immune dysfunction, a key aspect in ACLF, which drives organ failure and increases the risk of secondary infections. However, results of the scheduled interim analysis surprisingly failed to proof efficacy not only in the overall cohort, but also in various subpopulations. After futility analysis reaching significance within the planned sample size was deemed unlikely also because there was a trend to decreased survival after 90 days. The Data and Safety Monitoring board therefore recommended terminating the recruitment. Nevertheless, results are highly relevant as they speaks against the widespread believe that G-CSF modulates the disease course of end-stage liver disease. G-CSF was used in daily praxis in approximately 25% of tertiary centres in Europe and Asia. It is apparent that results from the GRAFT trial will therefore change treatment strategies and impacts on the further studies evaluating this type of therapy. The fact that the results from the interim analysis were accepted as an oral presentation in a presidential plenary session and got awarded with the international researcher award at the worldwide largest hepatology conference, AASLD 2019, emphasizes the relevance of these data in the global hepatology community.
Projektbezogene Publikationen (Auswahl)
- Granulocyte-Colony Stimulating Factor (G-CSF) to treat acute-on-chronic liver failure a multicenter randomized trial (GRAFT study): Interim analysis of the first randomized European trial. Hepatology; 70(S1):1476
Engelmann, C. et al.
(Siehe online unter https://doi.org/10.1002/hep.30940) - The current status of stem and immune cell mobilisation through granulocyte-colony stimulating factor (G-CSF) for ACLF. Seminars in Liver Liver Disease 2021
Engelmann C et al.
(Siehe online unter https://doi.org/10.1055/s-0041-1723034)
