Srinagesh, Hrishikesh K. and Ozbek, Umut and Kapoor, Urvi and Ayuk, Francis and Aziz, Mina and Ben-David, Kaitlyn and Choe, Hannah K. and DeFilipp, Zachariah and Etra, Aaron and Grupp, Stephan A. and Hartwell, Matthew J. and Hexner, Elizabeth O. and Hogan, William J. and Karol, Alexander B. and Kasikis, Stelios and Kitko, Carrie L. and Kowalyk, Steven and Lin, Jung-Yi and Major-Monfried, Hannah and Mielke, Stephan and Merli, Pietro and Morales, George and Ordemann, Rainer and Pulsipher, Michael A. and Qayed, Muna and Reddy, Pavan and Reshef, Ran and Roesler, Wolf and Sandhu, Karamjeet S. and Schechter, Tal and Shah, Jay and Sigel, Keith and Weber, Daniela and Woelfl, Matthias and Wudhikarn, Kitsada and Young, Rachel and Levine, John E. and Ferrara, James L. M. (2019) The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease. BLOOD ADVANCES, 3 (23). pp. 4034-4042. ISSN 2473-9529, 2473-9537
Full text not available from this repository. (Request a copy)Abstract
The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD). We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < .0001) and nonresponders (65% vs 25%, P < .0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0.290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE GVHD; END-POINT; THERAPY; RISK; SURVIVAL; SCORE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Transplantationszentrum |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 07:49 |
| Last Modified: | 20 Mar 2020 07:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25683 |
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