{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:51:37Z","timestamp":1785408697906,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,13]]},"group-title":"Oncology","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["P01 CA039542"],"award-info":[{"award-number":["P01 CA039542"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 CA196521"],"award-info":[{"award-number":["P30 CA196521"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21 HL177578"],"award-info":[{"award-number":["R21 HL177578"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R38AI181012-01"],"award-info":[{"award-number":["1R38AI181012-01"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Pediatric Cancer Foundation"},{"name":"Solomon and Gillespie Fund"},{"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00826gz80","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Approximately 30% of patients with acute graft-versus-host disease (GVHD) develop steroid-refractory disease and have very poor outcomes. Ruxolitinib has become the standard of care for steroid-refractory acute GVHD, but it is unclear which patients derive benefit. The MAGIC Composite Score (MCS), an algorithm that combines clinical symptoms and biomarkers, has been validated to predict outcomes at the start of primary GVHD treatment. Here, we evaluated its performance at the initiation of second-line treatment in 278 patients. MCS stratified patients into three risk groups (MCS1-3), with the majority (88%) classified as intermediate or high risk. Increasing MCS score was associated with progressively higher 1-year non-relapse mortality (NRM) rates (16%, 41%, and 73%; p&lt;0.001), lower 1-year survival (77%, 56%, and 24%; p&lt;0.001), and lower complete response (CR) rates at day 28 (47%, 38%, and 20%, respectively; p&lt;0.01). The area under the receiver operating characteristic curve (AUROC) for 1-year NRM was significantly higher with MCS compared to clinical symptoms alone (0.70 vs. 0.63; p=0.023). Among patients treated with ruxolitinib, higher MCS similarly predicted higher NRM and lower survival and CR rates. Patients classified as MCS2\/3 had poor outcomes despite ruxolitinib, underscoring the need for novel therapies in this patient population. In conclusion the MCS is an accurate predictor of outcomes for patients who require second-line treatment and may be of use as an eligibility criterion for future clinical trials in this high-risk population.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>MAGIC Composite Scores that integrate clinical symptoms and biomarker scores predict outcomes of second-line therapy for acute GVHD more accurately than clinical symptoms alone.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>MCS identifies patients with high NRM despite treatment with ruxolitinib.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.09.26357664","type":"posted-content","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:55:33Z","timestamp":1784008533000},"source":"Crossref","is-referenced-by-count":0,"title":["MAGIC Composite Score Predicts Outcomes of Second-Line Therapy for Acute GVHD"],"prefix":"10.64898","author":[{"given":"Tara","family":"Sebastian","sequence":"first","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Internal Medicine III, University of Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Etra","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Vasova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and University Hospital Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Ayuk","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah K.","family":"Choe","sequence":"additional","affiliation":[{"name":"Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachariah","family":"DeFilipp","sequence":"additional","affiliation":[{"name":"Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Quagliarella","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and of Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karni","family":"Bedirian","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcio Augusto","family":"Diniz","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paibel","family":"Aguayo-Hiraldo","sequence":"additional","affiliation":[{"name":"Division of Bone Marrow Transplantation, Children\u2019s Hospital Los Angeles, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bader","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna","family":"Baez","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantiya","family":"Chanswangphuwana","sequence":"additional","affiliation":[{"name":"Division of Hematology and Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Eng","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Francke","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth O.","family":"Hexner","sequence":"additional","affiliation":[{"name":"Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Katsivelos","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L.","family":"Kitko","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology Division, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Kraus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis E.","family":"Louloudis","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Morales","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryotaro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Hematopoietic Cell Transplantation, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"Qayed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Reddy","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Dan Duncan Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Reshef","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology and Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Schechter","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology\/Blood and Marrow Transplant, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"W\u00f6lfl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Levine","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.M","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071602250973000_2026.07.09.26357664v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337"},{"issue":"4","key":"2026071602250973000_2026.07.09.26357664v1.2","doi-asserted-by":"crossref","first-page":"101400","DOI":"10.1016\/j.beha.2022.101400","article-title":"Acute GVHD: New approaches to clinical trial monitoring","volume":"35","year":"2022","journal-title":"Best Pract Res Clin Haematol"},{"key":"2026071602250973000_2026.07.09.26357664v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60237-3"},{"issue":"9","key":"2026071602250973000_2026.07.09.26357664v1.4","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1182\/blood.2024025106","article-title":"Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD","volume":"144","year":"2024","journal-title":"Blood"},{"issue":"13","key":"2026071602250973000_2026.07.09.26357664v1.5","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1182\/bloodadvances.2024012561","article-title":"The MAGIC algorithm probability predicts treatment response and long-term outcomes to second-line therapy for acute graft-versus-host disease","volume":"8","year":"2024","journal-title":"Blood Adv"},{"key":"2026071602250973000_2026.07.09.26357664v1.6","doi-asserted-by":"crossref","first-page":"1211171","DOI":"10.3389\/fimmu.2023.1211171","article-title":"Second-line therapy for patients with steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis of randomized controlled trials","volume":"14","year":"2023","journal-title":"Front Immunol"},{"key":"2026071602250973000_2026.07.09.26357664v1.7","first-page":"601953","article-title":"Steroid-refractory acute graft-versus-host disease: predictors and outcomes","volume":"2011","year":"2011","journal-title":"Adv Hematol"},{"key":"2026071602250973000_2026.07.09.26357664v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2012.04.005"},{"issue":"10","key":"2026071602250973000_2026.07.09.26357664v1.9","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1038\/s41409-022-01741-3","article-title":"Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract","volume":"57","year":"2022","journal-title":"Bone Marrow Transplant"},{"key":"2026071602250973000_2026.07.09.26357664v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917635"},{"key":"2026071602250973000_2026.07.09.26357664v1.11","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020004823"},{"issue":"2","key":"2026071602250973000_2026.07.09.26357664v1.12","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1634\/theoncologist.2019-0627","article-title":"FDA approval summary: ruxolitinib for treatment of steroid-refractory acute graft-versus-host disease","volume":"25","year":"2020","journal-title":"Oncologist"},{"issue":"34","key":"2026071602250973000_2026.07.09.26357664v1.13","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1200\/JCO-25-00809","article-title":"Ruxolitinib versus best available therapy in patients with steroid-refractory acute graft-versus-host disease: final analysis from the randomized phase III REACH2 trial","volume":"43","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026071602250973000_2026.07.09.26357664v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.01.001"},{"key":"2026071602250973000_2026.07.09.26357664v1.15","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.220970"},{"issue":"1","key":"2026071602250973000_2026.07.09.26357664v1.16","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1016\/S2352-3026(14)00035-0","article-title":"et al; Blood and Marrow Transplant Clinical Trials Network. A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study","volume":"2","year":"2015","journal-title":"Lancet Haematol"},{"issue":"17","key":"2026071602250973000_2026.07.09.26357664v1.17","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1182\/bloodadvances.2023009929","article-title":"The utility of biomarkers in acute graft-versus-host disease prognostication","volume":"7","year":"2023","journal-title":"Blood Adv"},{"issue":"22","key":"2026071602250973000_2026.07.09.26357664v1.18","first-page":"2771","article-title":"Prognostic value of blood biomarkers in steroid-refractory or steroid-dependent acute graft-versus-host disease: a REACH2 analysis","volume":"141","year":"2023","journal-title":"Blood"},{"key":"2026071602250973000_2026.07.09.26357664v1.19","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89798"},{"key":"2026071602250973000_2026.07.09.26357664v1.20","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020214"},{"key":"2026071602250973000_2026.07.09.26357664v1.21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-01-822957"},{"key":"2026071602250973000_2026.07.09.26357664v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn326"},{"key":"2026071602250973000_2026.07.09.26357664v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.09.001"},{"issue":"308","key":"2026071602250973000_2026.07.09.26357664v1.24","first-page":"308r","article-title":"ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease","volume":"7","year":"2015","journal-title":"Sci Transl Med"},{"key":"2026071602250973000_2026.07.09.26357664v1.25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99261"},{"key":"2026071602250973000_2026.07.09.26357664v1.26","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176350951"},{"key":"2026071602250973000_2026.07.09.26357664v1.27","doi-asserted-by":"publisher","DOI":"10.2307\/2281868"},{"key":"2026071602250973000_2026.07.09.26357664v1.28","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177011454"},{"key":"2026071602250973000_2026.07.09.26357664v1.29","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2026071602250973000_2026.07.09.26357664v1.30","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5958"},{"key":"2026071602250973000_2026.07.09.26357664v1.31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI155880"},{"key":"2026071602250973000_2026.07.09.26357664v1.32","doi-asserted-by":"publisher","DOI":"10.1080\/003655201750305495"},{"issue":"7","key":"2026071602250973000_2026.07.09.26357664v1.33","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1182\/bloodadvances.2025017189","article-title":"Differential effects of GVHD therapies on intestinal epithelium","volume":"10","year":"2026","journal-title":"Blood Adv"},{"issue":"1","key":"2026071602250973000_2026.07.09.26357664v1.34","first-page":"45","article-title":"The MAGIC composite response: a novel end point integrating clinical and biomarker parameters for acute graft-versus-host disease","volume":"146","year":"2025","journal-title":"Blood"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.09.26357664","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:25:22Z","timestamp":1784193922000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.07.09.26357664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":34,"URL":"https:\/\/doi.org\/10.64898\/2026.07.09.26357664","relation":{},"subject":[],"published":{"date-parts":[[2026,7,13]]},"subtype":"preprint"}}