Spyrou, Nikolaos and Akahoshi, Yu and Kowalyk, Steven and Morales, George and Beheshti, Rahnuma and Aguayo-Hiraldo, Paibel and Al Malki, Monzr M. and Ayuk, Francis and Bader, Peter and Baez, Janna and Capellini, Alexandra and Choe, Hannah and Defilipp, Zachariah and Eder, Matthias and Eng, Gilbert and Etra, Aaron and Gleich, Sigrun and Grupp, Stephan A. and Hexner, Elizabeth and Hoepting, Matthias and Hogan, William J. and Kasikis, Stelios and Katsivelos, Nikolaos and Khan, Alina and Kitko, Carrie L. and Kraus, Sabrina and Kwon, Deukwoo and Merli, Pietro and Portelli, Joseph and Qayed, Muna and Reshef, Ran and Schechter, Tal and Vasova, Ingrid and Woefl, Matthias and Wudhikarn, Kitsada and Young, Rachel and Holler, Ernst and Chen, Yi-Bin and Nakamura, Ryotaro and Levine, John E. and Ferrara, James L. M. (2024) A Day 14 Endpoint for Acute GVHD Clinical Trials. TRANSPLANTATION AND CELLULAR THERAPY, 30 (4). pp. 421-432. ISSN 2666-6375, 2666-6367
Full text not available from this repository. (Request a copy)Abstract
The overall response rate (ORR) 28 days after treatment has been adopted as the primary endpoint for clinical trials of acute graft versus host disease (GVHD). However, physicians often need to modify immunosuppression earlier than day (D) 28, and non -relapse mortality (NRM) does not always correlate with ORR at D28. We studied 1144 patients that received systemic treatment for GVHD in the Mount Sinai Acute GVHD International Consortium (MAGIC) and divided them into a training set (n=764) and a validation set (n=380). We used a recursive partitioning algorithm to create a Mount Sinai model that classi fies patients into favorable or unfavorable groups that predicted 12 month NRM according to overall GVHD grade at both onset and D14. In the Mount Sinai model grade II GVHD at D14 was unfavorable for grade III/IV GVHD at onset and predicted NRM as well as the D28 standard response model. The MAGIC algorithm probability (MAP) is a validated score that combines the serum concentrations of suppression of tumorigenicity 2 (ST2) and regenerating islet -derived 3 -alpha (REG3 a) to predict NRM. Inclusion of the D14 MAP biomarker score with the D14 Mount Sinai model created three distinct groups (good, intermediate, poor) with strikingly different NRM (8%, 35%, 76% respectively). This D14 MAGIC model displayed better AUC, sensitivity, positive and negative predictive value, and net bene fit in decision curve analysis compared to the D28 standard response model. We conclude that this D14 MAGIC model could be useful in therapeutic decisions and may offer an improved endpoint for clinical trials of acute GVHD treatment. erapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; BIOMARKER; Acute GVHD; Biomarkers; Endpoints; Treatment response; Immunosuppression; Nonrelapse mortality; Competing risks; Surrogate; Composite; Machine learning; Competing risk; Time-dependent AUC; Decision curve analysis; Classification and regres-sion tree |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Aug 2025 06:33 |
| Last Modified: | 14 Aug 2025 06:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65642 |
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