The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
Year: 2019
Type: article
Study design: Observational Study
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.
Source: Blood Advances
Authors: Hrishikesh K. Srinagesh, Umut Özbek, Urvi Kapoor, Francis Ayuk, Mina Aziz, Kaitlyn Ben-David, Hannah K. Choe, Zachariah DeFilipp, Aaron Etra, Stephan A. Grupp, Matthew J. Hartwell, Elizabeth O. Hexner, William J. Hogan, Alexander B. Karol, Stelios Kasikis, Carrie L. Kitko, Steven Kowalyk, Jung-Yi Lin, Hannah Major-Monfried, Stephan Mielke, Pietro Merli, George Morales, Rainer Ordemann, Michael A. Pulsipher, Muna Qayed, Pavan Reddy, Ran Reshef, Wolf Rösler, Karamjeet S. Sandhu, Tal Schechter, Jay Shah, Keith Sigel, Daniela Weber, Matthias Wölfl, Kitsada Wudhikarn, Rachel Young, John E. Levine, James L. M. Ferrara
Institutions: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, University Medical Center Hamburg-Eppendorf, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Massachusetts General Hospital, Children's Hospital of Philadelphia, Abramson Cancer Center, University of Pennsylvania, Mayo Clinic, Vanderbilt University Medical Center, Karolinska University Hospital, University of Würzburg, Karolinska Institutet, Universitätsklinikum Würzburg, Bambino Gesù Children's Hospital, University Hospital Carl Gustav Carus, Technische Universität Dresden, Children's Hospital of Los Angeles, Emory University, Children's Healthcare of Atlanta, University of Michigan, Columbia University Irving Medical Center, Columbia University, Universitätsklinikum Erlangen, City Of Hope National Medical Center, City of Hope, University of Toronto, Hospital for Sick Children, University of Regensburg, Chulalongkorn University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W2992108607