Original ArticlesHistologic Grade 1 Is Associated With Increased Nonrelapsed Mortality in Lower Gastrointestinal Graft Versus Host DiseaseIm, Jin S. MD, PhD*; Abraham, Susan C. MD†; Saliba, Rima M. PhD*; Rondon, Gabriela MD*; Ross, William A. MD‡; Rashid, Asif MD, PhD†; Shpall, Elizabeth J. MD*; Popat, Uday MD*; Qazilbash, Muzaffar H. MD*; Hosing, Chitra MD*; Oran, Betul MD*; Shah, Nina MD§; Tewari, Priti MD∥; Nieto, Yago MD*; Kebriaei, Partow MD*; Champlin, Richard E. MD*; Alousi, Amin M. MD*Author Information Departments of *Stem Cell Transplantation and Cellular Therapy †Pathology ‡Gastroenterology, The University of Texas M.D. Anderson Cancer Center §Department of Pediatric Oncology, Baylor College of Medicine, Houston, TX ∥Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Amin M. Alousi, MD, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D Anderson Cancer Center, 1515 Holcombe Blvd., Unit 423, Houston, TX (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: November 2017 - Volume 41 - Issue 11 - p 1483–1490 doi: 10.1097/PAS.0000000000000914 Buy SDC Metrics Abstract Histologic confirmation is considered a standard practice to diagnose gastrointestinal graft versus host disease (GI GVHD) and is often used in making treatment decisions. A histologic grade is often determined in cases that are diagnosed with GI GVHD. Although extensive crypt loss (histologic grade 4) is associated with high nonrelapse mortality (NRM), the prognostic value for the more common grade 1 is poorly understood. As clinical decisions are made on the degree of histologic evidence, it is important to establish its prognostic significance. Therefore, we evaluated 309 patients who underwent endoscopic biopsy for suspected GI GVHD within 6 months posttransplant between 2009 and 2012. The presence of histologic grade 1 was associated with increased NRM (hazard ratio=2.7, P=0.02) when compared with one of negative biopsy in patients with lower but not isolated upper GI GVHD. Multivariate competing-risk regression analysis confirmed the independent impact of histologic grade 1 in patients with early clinical stages of lower GI GVHD (stage 0 to 2) (hazard ratio=2.7, P=0.044). When compared with advanced histologic grades, histologic grade 1 did not lessen the adverse outcome for patients with advanced lower GI GVHD (stage 3 to 4) (cumulative incidence NRM of 84%). In conclusion, the presence of histologic grade 1 is associated with increased NRM in patients presenting with lower GI GVHD (stages 0 to 2) and is sufficient evidence for decision to initiate therapy. At the same time, histologic grade 1 does not lessen the markedly adverse impact of advanced lower GI GVHD (stage 3 to 4) and is not synonymous with “mild” GVHD. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.