title: The association of histologic grade with acute graft-versus-host disease response and outcomes.
abstract: Consensus criteria are routinely used to clinically grade acute graft-versus-host disease (GVHD). A histologic grading system for acute GVHD is available, but there are limited data on its correlation with clinical grade and hematopoietic cell transplantation (HCT) outcomes. Among 503 patients who underwent allogeneic HCT from 2005 to 2013, we identified 300 biopsy episodes of the skin and gastrointestinal (GI) tract in 231 patients. Histologic grade was correlated with clinical grade of GVHD, day 28 treatment response, and outcome. Both skin (R = 0.32) and GI (R = 0.61) histologic grade correlated with clinical grade (P < 0.001). On multivariable analysis, histologic grade (HR 0.87, P = 0.011) and clinical grade (HR 0.86, P = 0.008) were significantly associated with day 28-treatment response. A histologic grade lower than its associated clinical grade predicted for better response (HR 1.26, P = 0.027), while a histologic grade higher than associated clinical grade had no correlation with response (P = 0.89). Both clinical and histologic GVHD grade were significant predictors of non-relapse mortality (HR 1.47, P = 0.04 and HR 1.67, P = 0.002, respectively) and all-cause mortality (HR 1.57, P = 0.001 and HR 1.29, P = 0.046, respectively). Histologic GVHD grade thus is correlated with clinical grading and treatment response, and may play a role in further predicting severity and treatment response of acute GVHD.
authors.affiliation: Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Mayur
authors.initials: M
authors.lastname: Narkhede
authors.affiliation: Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rybicki
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Abounader
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Bolwell
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Dean
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Aaron T
authors.identifier: http://orcid.org/0000-0002-3422-1309
authors.initials: AT
authors.lastname: Gerds
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Rabi
authors.initials: R
authors.lastname: Hanna
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hill
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Jagadeesh
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Hien D
authors.initials: HD
authors.lastname: Liu
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Pohlman
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Navneet S
authors.initials: NS
authors.lastname: Majhail
authors.affiliation: Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Betty
authors.identifier: http://orcid.org/0000-0003-1252-6539
authors.initials: B
authors.lastname: Ky Hamilton
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002423:Cause of Death; D015897:Comorbidity; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult