ORIGINAL ARTICLE New classification of chronic GVHD: added clarity from the consensus diagnoses M Arora 1,2 , S Nagaraj 1,2 , J Witte 1,2 , TE DeFor 1,2 , M MacMillan 1,2 , LJ Burns 1,2 and DJ Weisdorf 1,2 1 Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, MN, USA and 2 Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA The Diagnosis and Staging Working Group of the NIH Consensus Development Project on Criteria for Clinical Trials in chronic GVHD (CGVHD) recently proposed criteria for diagnosis and assessment of overall CGVHD severity. We retrospectively reviewed 54 consecutive patients diagnosed with CGVHD between January 2002 and December 2005 after sibling donor transplant to assess the applicability of the new criteria in prognos- ticating survival and transplant-related mortality (TRM). A total of 8 patients (15%) were reclassified as late onset/ persistent or recurrent acute GVHD (late aGVHD), 15 (28%) had overlap syndrome and 31 (57%) had classic CGVHD. Three-year overall survival was worse in patients with late aGVHD (3-year probability 25% (95% CI 4–56%)) followed by overlap syndrome (3-year probability 87% (95% CI 56–96%)) and CGVHD (3-year probability 75% (95% CI 54–87%)); P ¼ 0.001. Among patients with overlap syndrome and CGVHD, a trend towards worse survival was seen in patients with severe disease (3-year probability 57.3% (95% CI 21–82%)) as compared to mild þ moderate disease (3-year probability 85.1% (95% CI 68–94)); P ¼ 0.1. This analysis, undertaken in a contemporary cohort of related donor recipients, indicates that the consensus guidelines are applicable to this population of CGVHD patients. Bone Marrow Transplantation (2009) 43, 149–153; doi:10.1038/bmt.2008.305; published online 15 September 2008 Keywords: CGVHD; classification; consensus guidelines Introduction Chronic GVHD (CGVHD) is a multiorgan disorder resembling autoimmune diseases, 1,2 and is the leading cause of late nonrelapse mortality (transplant-related mortality, TRM) after hematopoietic stem cell transplant (HSCT). 3 The disease usually, but not always manifests after 100 days post transplant. Clinical syndromes resem- bling acute GVHD (aGVHD) 4,5 are increasingly recognized beyond 100 days after HSCT 6,7 and may be labeled as CGVHD. In addition, patients with aGVHD may progress to develop CGVHD with distinctive signs and symptoms of both acute and chronic GVHD. In addition, the old grading system of limited versus extensive GVHD was designed to identify patients needing systemic immune suppression and does not capture the severity of individual organ involvement. 2 Several grading schemes 8–11 can predict survival following CGVHD. However, all lack consistent scoring and assessment of each involved organ to determine the overall severity of the disease. Recognizing these limitations, the diagnosis and staging working group of the NIH Consensus Development Project on CGVHD 1 proposed standard criteria for diagnosis, organ scoring and global assessment of CGVHD severity. We retrospectively reviewed 54 consecutive patients with CGVHD to assess the applicability of these criteria. Materials and methods All consecutive patients undergoing sibling donor trans- plant between January 2002 and December 2005 (n ¼ 197) and diagnosed with CGVHD (n ¼ 54) were eligible for this study. All patients were enrolled into protocols approved by Institutional Review Board of University of Minnesota and patients or their guardians signed informed consents. This retrospective review of patients with CGVHD was also approved by the Institutional Review Board of University of Minnesota. Demographic information regarding all patients undergoing a hematopoietic cell transplant is prospectively entered in the University of Minnesota Bone Marrow Transplant Database. This includes dates of diagnosis of CGVHD, type of onset and organs involved at baseline, relapse, survival and cause of death. This was supplemented by chart reviews for CGVHD-specific information including presenting symp- toms and signs in the organs involved including degree of functional impairment, performance status, biopsy and/or pertinent lab results (including liver function tests, WBC count with differential, hemoglobin, plt count, wt, pulmonary function tests, Schirmer’s test), treatment given, Received 15 May 2008; revised 25 July 2008; accepted 29 July 2008; published online 15 September 2008 Correspondence: Dr M Arora, Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Mayo Mail Code 480, 420 Delaware Street SE, Minneapolis, MN 55455, USA. E-mail: arora005@umn.edu Bone Marrow Transplantation (2009) 43, 149–153 & 2009 Macmillan Publishers Limited All rights reserved 0268-3369/09 $32.00 www.nature.com/bmt