ORIGINAL ARTICLE Risk factors and organ involvement of chronic GVHD in Japan J Kanda 1 , H Nakasone 1 , Y Atsuta 2 , T Toubai 3 , H Yokoyama 4 , T Fukuda 5 , S Taniguchi 6 , K Ohashi 7 , H Ogawa 8 , T Eto 9 , K Miyamura 10 , Y Morishima 11 , T Nagamura-Inoue 12 , H Sakamaki 7 and M Murata 13 on behalf of the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II–IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints. Bone Marrow Transplantation (2014) 49, 228–235; doi:10.1038/bmt.2013.151; published online 30 September 2013 Keywords: chronic GVHD; unrelated cord blood; acute GVHD; risk factors INTRODUCTION Chronic GVHD is a serious complication that affects the survival and quality of life of long-term survivors after allogeneic hemato- poietic SCT. 1–3 Various pre- and post-transplant risk factors associated with chronic GVHD have been identified, mostly in transplantations using BM and PBSC grafts from related or unrelated donors. 2,3 Several studies have reported a history of acute GVHD to be a strong risk factor that is consistently associated with chronic GVHD development. 4–8 Other identified risk factors include the following: female donor and male recipient, 4,6 use of PBSC grafts, 6,9–13 older patient, 4,6–8 older donor, 6,7 transplantation from a mismatched or unrelated donor, 5,6,14 diagnosis of CML 4,7,8 and absence of anti-thymocyte globulin (ATG) use. 15 The number of unrelated cord blood (U-CB) transplantations performed has rapidly increased during the past decade. However, few studies have compared the incidences and risk factors of chronic GVHD and its organ-specific symptoms in adult patients receiving U-CB and other available grafts, including related or unrelated BM/PBSC grafts. 16,17 Therefore, we conducted a retrospective study using national registry data involving 4818 patients who underwent allogeneic transplantation. This study aimed to evaluate the incidence and risk factors of chronic GVHD, and the prevalence of chronic GVHD organ involvement in patients who received transplantation using various types of graft, including U-CB. MATERIALS AND METHODS Data collection Data for 54 072 patients who had received auto-SCT or allo-SCT by December 31, 2009 were provided by the Transplant Registry Unified Management Program (TRUMP). 18 We included 4993 adult patients who had: (1) received allogeneic transplantation for hematologic malignancies; (2) received their first SCT; (3) used the same questionnaire form involving chronic GVHD organ involvement (skin, oral cavity, eye, liver, lung, joint, intestine/genitals and other manifestations; 2006–2009 for transplanta- tions using BM or PBSC grafts and 2007–2009 for transplantations using U-CB units); (4) achieved neutrophil engraftment; (5) survived for at least 100 days; and (6) received the following: (a) a related BM or PBSC graft (R- BM/PB), (b) an unrelated BM (U-BM) or (c) a single U-CB unit. Donation of peripheral blood by unrelated volunteers was permitted for the first time in Japan in 2011. The following patients were excluded: (1) patients who received ex vivo T-cell-depleted grafts (n ¼ 26) and (2) patients who lacked data on acute or chronic GVHD (n ¼ 149). Thus, 4818 patients were included in this study, which was approved by the TRUMP Data Management Committees and by the institutional review board of the Nagoya University Graduate School of Medicine, where this study was performed. Histocompatibility Histocompatibility data for the HLA-A, HLA-B and HLA-DR loci were obtained through reports acquired from the institution where the transplantation was performed or from the cord blood bank. HLA 1 Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 2 Department of Hematopoietic Stem Cell Transplantation Data Management/ Biostatistics, Nagoya University School of Medicine, Nagoya, Japan; 3 Division of Hematology & Oncology, Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, MI, USA; 4 Division of Clinical Oncology and Hematology, Jikei University School of Medicine, Tokyo, Japan; 5 Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan; 6 Department of Hematology, Toranomon Hospital, Tokyo, Japan; 7 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan; 8 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan; 9 Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan; 10 Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan; 11 Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan; 12 Department of Cell Processing & Transfusion, Research Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan and 13 Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Correspondence: Dr J Kanda, Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama City 330-8503, Japan. E-mail: jkandajp@gmail.com Received 25 April 2013; revised 10 August 2013; accepted 12 August 2013; published online 30 September 2013 Bone Marrow Transplantation (2014) 49, 228–235 & 2014 Macmillan Publishers Limited All rights reserved 0268-3369/14 www.nature.com/bmt