Flares of acute graft-versus-host disease: a Mount Sinai Acute GVHD International Consortium analysis.

Akahoshi Y, Spyrou N, Hoepting M, Aguayo-Hiraldo P, Ayuk F, Chanswangphuwana C, Choe HK, Eder M, Etra AM, Grupp SA, Hexner EO, Hogan WJ, Kitko CL, Kraus S, Al Malki MM, Merli P, Qayed M, Reshef R, Schechter T, Ullrich E, Vasova I, Wölfl M, Zeiser R, Baez J, Beheshti R, Eng G, Gleich S, Kasikis S, Katsivelos N, Kowalyk S, Morales G, Young R, DeFilipp Z, Ferrara JL, Levine JE, Nakamura R (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 8

Pages Range: 2047-2057

Journal Issue: 8

DOI: 10.1182/bloodadvances.2023012091

Abstract

The absence of a standardized definition for graft-versus-host disease (GVHD) flares and data on its clinical course are significant concerns. We retrospectively evaluated 968 patients across 23 Mount Sinai Acute GVHD International Consortium (MAGIC) transplant centers who achieved complete response (CR) or very good partial response (VGPR) within 4 weeks of treatment. The cumulative incidence of flares within 6 months was 22%, and flares were associated with a higher risk of nonrelapse mortality (NRM; adjusted hazard ratio [aHR], 4.84; 95% confidence interval [CI], 3.19-7.36; P < .001). Flares were more severe (grades 3/4, 41% vs 16%; P < .001) and had more frequent lower gastrointestinal (LGI) involvement (55% vs 32%; P < .001) than the initial GVHD. At CR/VGPR, elevated MAGIC biomarkers predicted the future occurrence of a flare, along with its severity and LGI involvement. In multivariate analyses, higher Ann Arbor (AA) biomarker scores at CR/VGPR were significant risk factors for flares (AA2 vs AA1: aHR, 1.81 [95% CI, 1.32-2.48; P = .001]; AA3 vs AA1: aHR, 3.14 [95% CI, 1.98-4.98; P < .001]), as were early response to initial treatment (aHR, 1.84; 95% CI, 1.21-2.80; P = .004) and HLA-mismatched unrelated donor (aHR, 1.74; 95% CI, 1.00-3.02; P = .049). MAGIC biomarkers also stratified the risk of NRM both at CR/VGPR and at the time of flare. We conclude that GVHD flares are common and carry a significant mortality risk. The occurrence of future flares can be predicted by serum biomarkers that may serve to guide adjustment and discontinuation of immunosuppression.

Authors with CRIS profile

Involved external institutions

Icahn School of Medicine at Mount Sinai United States (USA) (US) Universität Regensburg Germany (DE) University of Southern California (USC) United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย Thailand (TH) Ohio State University United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Children's Hospital of Philadelphia United States (USA) (US) Penn Medicine United States (USA) (US) Mayo Clinic United States (USA) (US) Vanderbilt University United States (USA) (US) Universitätsklinikum Würzburg Germany (DE) City of Hope Medical Center United States (USA) (US) Ospedale Pediatrico Bambino Gesu Italy (IT) Emory University United States (USA) (US) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) The Hospital for Sick Children (SickKids) Canada (CA) Goethe-Universität Frankfurt am Main Germany (DE) Universitätsklinikum Freiburg Germany (DE) Massachusetts General Hospital United States (USA) (US)

How to cite

APA:

Akahoshi, Y., Spyrou, N., Hoepting, M., Aguayo-Hiraldo, P., Ayuk, F., Chanswangphuwana, C.,... Nakamura, R. (2024). Flares of acute graft-versus-host disease: a Mount Sinai Acute GVHD International Consortium analysis. Blood Advances, 8(8), 2047-2057. https://doi.org/10.1182/bloodadvances.2023012091

MLA:

Akahoshi, Yu, et al. "Flares of acute graft-versus-host disease: a Mount Sinai Acute GVHD International Consortium analysis." Blood Advances 8.8 (2024): 2047-2057.

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