Disease Risk and GVHD Biomarkers Can Stratify Patients For Risk of Relapse and Non-Relapse Mortality Post Hematopoietic Cell Transplant

• Type of Material: Article
• Authors: Mina D. Aziz, Icahn School of Medicine at Mount Sinai; Jay Shah, Emory University; Urvi Kapoor, Icahn School of Medicine at Mount Sinai; Christina Dimopoulos, Icahn School of Medicine at Mount Sinai; Sarah Anand, University of Michigan; Allan Augustine, Icahn School of Medicine at Mount Sinai; Muna Qayed, Emory University; Umut Ozbek, Icahn School of Medicine at Mount Sinai; James L. M. Ferrara, Icahn School of Medicine at Mount Sinai; John E. Levine, Icahn School of Medicine at Mount Sinai
• Language: English
• Date: 2020-02-04
• Publisher: Springer Nature [academic journals on nature.com]
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, The Author(s), under exclusive licence to Springer Nature Limited
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41375-020-0726-z
• Title of Journal or Parent Work: LEUKEMIA
• Volume: 34
• Issue: 7
• Start Page: 1898
• End Page: 1906
• Grant/Funding Information: Supported by grants (R21CA173459, P01CA03942, and P30CA196521) from the National Cancer Institute, an American Cancer Society Clinical Research Professorship (to Dr. Ferrara) and a Doris Duke Charitable Foundation Clinical Research Mentorship (to Dr. Aziz and Dr. Hartwell).
• Keywords: non-relapse mortality (NRM); graft-versus-leukemia (GVL); biomarkers; asymptomatic; MAGIC algorithm probability (MAP); graft-vs-host disease (GVHD); immunosuppression; allogeneic hematopoietic cell transplant (HCT)

Abstract

The graft-versus-leukemia (GVL) effect after allogeneic hematopoietic cell transplant (HCT) can prevent relapse but the risk of severe graft-vs-host disease (GVHD) leads to prolonged intensive immunosuppression and possible blunting of the GVL effect. Strategies to reduce immunosuppression in order to prevent relapse have been offset by increases in severe GVHD and non-relapse mortality (NRM). We recently validated the MAGIC algorithm probability (MAP) that predicts the risk for severe GVHD and NRM in asymptomatic patients using serum biomarkers. In this study we tested whether the MAP could identify patients whose risk for relapse is higher than their risk for severe GVHD and NRM. The multicenter study population (n=1604) was divided into two cohorts: historical (2006–2015, n=702) and current (2015–2017, n=902) with similar non-relapse mortality, relapse, and survival. On day 28 post-HCT, patients who had not developed GVHD (75% of the population) and who possessed a low MAP were at much higher risk for relapse (24%) than severe GVHD and NRM (16% and 9%); this difference was even more pronounced in patients with a high disease risk index (relapse 33%, NRM 9%). Such patients are good candidates to test relapse prevention strategies that might enhance GVL.