Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC

Akahoshi Y, Inamoto Y, Spyrou N, Nakasone H, Diniz MA, Asada N, Ayuk F, Choe HK, Doki N, Eto T, Etra AM, Hexner EO, Hiramoto N, Hogan WJ, Holler E, Kataoka K, Kawakita T, Tanaka M, Tanaka T, Uchida N, Vasova I, Yoshihara S, Ishimaru F, Fukuda T, Chen YB, Kanda J, Nakamura R, Atsuta Y, Ferrara JL, Kanda Y, Levine JE, Teshima T (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 9

Pages Range: 4640-4653

Journal Issue: 18

DOI: 10.1182/bloodadvances.2025016233

Abstract

Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials.

Authors with CRIS profile

Involved external institutions

City of Hope Medical Center United States (USA) (US) Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) / 一般社団法人 日本造血細胞移植データセンター Japan (JP) Icahn School of Medicine at Mount Sinai United States (USA) (US) Fujita Health University Japan (JP) Hyogo Medical University Hospital / 兵庫医科大学病院 Japan (JP) Japanese Red Cross Society Japan (JP) National Cancer Center Hospital Japan (JP) Massachusetts General Hospital United States (USA) (US) Jichi Medical University / 自治医科大学 Japan (JP) Okayama University Hospital Japan (JP) Hamanomachi Hospital / 浜の町病院 Japan (JP) Kobe City Medical Center Japan (JP) Mayo Clinic United States (USA) (US) Universität Regensburg Germany (DE) National Cancer Centre Japan (NCC) / 国立研究開発法人国立がん研究センター Japan (JP) National Hospital Organization Kumamoto Medical Center / 熊本医療センター Japan (JP) Kanagawa Prefectural Hospital / Kanagawa Cancer Center / 神奈川県立がんセンター Japan (JP) Toranomon Hospital Japan (JP) Penn Medicine United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Ohio State University United States (USA) (US) Tokyo Metropolitan Komagome Hospital / 駒込病院 Japan (JP)

How to cite

APA:

Akahoshi, Y., Inamoto, Y., Spyrou, N., Nakasone, H., Diniz, M.A., Asada, N.,... Teshima, T. (2025). Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC. Blood Advances, 9(18), 4640-4653. https://doi.org/10.1182/bloodadvances.2025016233

MLA:

Akahoshi, Yu, et al. "Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC." Blood Advances 9.18 (2025): 4640-4653.

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