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国立がん研究センター 中央病院

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Department of Hematopoietic Stem Cell Transplantation

Takahiro Fukuda, Sung-Won Kim, Saiko Kurosawa, Shigeo Fuji, Yoshihiro Inamoto, Takashi Tanaka, Ayumu Ito

Introduction

At the National Cancer Center Hospital (NCCH), the Department of Hematopoietic Stem Cell Transplantation (HSCT) specializes in patients who undergo allogeneic or autologous HSCT. Twenty-six beds in ward 12B and an additional three beds in ward 11A, which are filtered by a central high-efficiency particulate air filtration system, are solely dedicated to our Transplant Unit.

Routine activities

Table 1. Number of each type of HSCT

Table 1. Number of each type of HSCT

Table 2. Number of patients who underwent HSCT in 2016

Table 2. Number of patients who underwent HSCT in 2016

Seven staff physicians (Drs. Kim, Kurosawa, Fuji, Inamoto, Tanaka, Ito, and Fukuda) and three chief residents (Drs. Ohnishi, Kawajiri, and Takemura) participate in the transplant program. Children who have undergone HSCT are managed in collaboration with Dr. Ogawa, the chief of the Department of Pediatric Oncology, and the transplant team. In 2016, a total of 101 transplantations were performed at the 12B and 12A transplant units. The numbers of each type of HCST between 2012 and 2016 are shown in Table 1, and the numbers of patients according to disease type are shown in Table 2.

At the weekly conference on Monday afternoons, in collaboration with doctors of the Department of Hematology and the Department of Pediatric Oncology, about 30 hospitalized HSCT patients and those who have been referred for HSCT, are reviewed for clinical management and a decision regarding their eligibility for HSCT. The transplant unit is staffed by 24 nurses trained in oncology and specialized supportive care for HSCT patients. The nursing unit has been assuming leadership in an effort to facilitate improved care for graft-versus-host disease (GVHD), and the establishment of a Long-term Follow-up Unit (LTFU) for the education of patients and their family members. In 2016, 419 patients visited our LTFU clinic. At the weekly 12B ward meeting on Friday afternoons, all HSCT patients are reviewed in detail by all transplant team members including doctors, nurses, pharmacists, the nutritional support team, clinical research coordinators, and the Hematopoietic Cell Transplant Coordinator (HCTC).

Research activities and Clinical trials

We have done nationwide studies focusing on HSCT for patients with adult T-cell leukemia. Our study suggested that the use of mogamulizumab, anti-CCR4 antibody, before allogeneic HSCT significantly worsened the clinical outcome, mainly due to an increased risk of acute GVHD (Fuji et al. J Clin Oncol, 2016). We published a recent improvement in non-relapse mortality after allo-HSCT in our hospital (Tanaka et al. BMT, 2016). We also published a decision analysis of post-remission therapy in acute myeloid leukemia (AML) according to genetic risk (Kurosawa et al. BBMT, 2016). In 2016, we published 48 articles in peer-reviewed international journals.

List of papers published in 2016

Journal

1.Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, Otsuka E, Henzan H, Kato K, Tomoyose T, Yamamoto H, Kurosawa S, Matsuoka K, Yamaguchi T, Fukuda T. Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality. J Clin Oncol, 34:3426-3433, 2016

2.Kurosawa S, Yamaguchi H, Yamaguchi T, Fukunaga K, Yui S, Wakita S, Kanamori H, Usuki K, Uoshima N, Yanada M, Shono K, Ueki T, Mizuno I, Yano S, Takeuchi J, Kanda J, Okamura H, Inamoto Y, Inokuchi K, Fukuda T. Decision Analysis of Postremission Therapy in Cytogenetically Intermediate-Risk Acute Myeloid Leukemia: The Impact of FLT3 Internal Tandem Duplication, Nucleophosmin, and CCAAT/Enhancer Binding Protein Alpha. Biol Blood Marrow Transplant, 22時11分25-1132, 2016

3.Tanaka Y, Kurosawa S, Tajima K, Tanaka T, Ito R, Inoue Y, Okinaka K, Inamoto Y, Fuji S, Kim SW, Tanosaki R, Yamashita T, Fukuda T. Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant, 51:553-559, 2016

4.Tanaka T, Inamoto Y, Yamashita T, Fuji S, Okinaka K, Kurosawa S, Kim S-W, Tanosaki R, Fukuda T. Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant, 22:919-924, 2016

5.Matsumura-Kimoto Y, Inamoto Y, Tajima K, Kawajiri A, Tanaka T, Hirakawa T, Ino K, Asao Y, Tamogami H, Kono C, Takeda W, Okinaka K, Fuji S, Kurosawa S, Kim S-W, Tanosaki R, Yamashita T, Fukuda T. Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant, 22時11分02-1107, 2016

6.Inoue Y, Fuji S, Tanosaki R, Fukuda T. Pretransplant mogamulizumab against ATLL might increase the risk of acute GVHD and non-relapse mortality. Bone Marrow Transplant, 51:725-727, 2016

7.Kuriyama K, Fuji S, Inamoto Y, Tajima K, Tanaka T, Inoue Y, Ito R, Hayashi Y, Ito A, Kurosawa S, Kim S-W, Yamashita T, Fukuda T. Impact of low-dose rabbit anti-thymocyte globulin in unrelated hematopoietic stem cell transplantation. Int J Hematol, 13時45分3-460, 2016

8.Makita S, Fuji S, Takano K, Tanaka T, Inoue Y, Ito R, Ito A, Hayashi Y, Tajima K, Okinaka K, Kurosawa S, Kim S-W, Yamashita T, Tanosaki R, Tobinai K, Fukuda T. Clinical Outcomes after Allogeneic Stem Cell Transplantation for Adult Lymphoblastic Lymphoma. J Clin Exp Hematop, 56:28-33, 2016

9.Ohmoto A, Fuji S, Miyagi-Maeshima A, Tajima K, Tanaka T, Ito R, Inoue Y, Okinaka K, Kurosawa S, Inamoto Y, Yamashita T, Taniguchi H, Makita S, Kitahara H, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tanosaki R, Tobinai K, Fukuda T, Kim SW. Prognostic factors in patients with relapsed or refractory diffuse large B-cell lymphoma who underwent autologous stem-cell transplantation. J Hematopoietic Cell Transplantation, 5:93-101, 2016

10.Fuji S, Kim SW, Yano S, Hagiwara S, Nakamae H, Hidaka M, Ito T, Ohashi K, Hatanaka K, Takami A, Kurosawa S, Yamashita T, Yamaguchi T, Fukuda T. A prospective multicenter study of unrelated bone marrow transplants using a reduced-intensity conditioning regimen with low-dose ATG-F. Bone Marrow Transplant, 51:451-453, 2016

11.Fuji S, Fujiwara H, Nakano N, Wake A, Inoue Y, Fukuda T, Hidaka M, Moriuchi Y, Miyamoto T, Uike N, Taguchi J, Eto T, Tomoyose T, Kondo T, Yamanoha A, Ichinohe T, Atsuta Y, Utsunomiya A. Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma. Bone Marrow Transplant, 51:205-211, 2016

12.Fuji S, Shindo T. Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma. Stem Cell Investig, 3:70, 2016

13.Fuji S, Loffler J, Einsele H, Kapp M. Immunotherapy for opportunistic infections: Current status and future perspectives. Virulence, 7:939-949, 2016

14.Fuji S, Rovo A, Ohashi K, Griffith M, Einsele H, Kapp M, Mohty M, Majhail NS, Engelhardt BG, Tichelli A, Savani BN. How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT. Bone Marrow Transplant, 51:1041-1049, 2016

15.Inamoto Y, Martin PJ, Flowers MED, Lee SJ, Carpenter PA, Warren EH, Geraghty DE, Lee N, Boeckh MJ, Storer BE, Levine DM, Fan W, Zhao L-P, Hansen JA. Genetic risk factors for sclerotic graft-versus-host disease. Blood, 128:1516-1524, 2016

16.Inamoto Y, Aki SZ, Carpenter PA, Storer BE, Sandmaier BM, Lee SJ, Martin PJ, Flowers MED. Confounding factors affecting the National Institutes of Health (NIH) chronic Graft-Versus-Host Disease Organ-Specific Score and global severity. Bone Marrow Transplant, 51:1350-1353, 2016

17.Inamoto Y, Kimura F, Kanda J, Sugita J, Ikegame K, Nakasone H, Nannya Y, Uchida N, Fukuda T, Yoshioka K, Ozawa Y, Kawano I, Atsuta Y, Kato K, Ichinohe T, Inoue M, Teshima T. Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica, 11時15分92-1602, 2016

18.Wakita S, Yamaguchi H, Ueki T, Usuki K, Kurosawa S, Kobayashi Y, Kawata E, Tajika K, Gomi S, Koizumi M, Fujiwara Y, Yui S, Fukunaga K, Ryotokuji T, Hirakawa T, Arai K, Kitano T, Kosaka F, Tamai H, Nakayama K, Fukuda T, Inokuchi K. Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia. Leukemia, 30:545-554, 2016

19.Ryotokuji T, Yamaguchi H, Ueki T, Usuki K, Kurosawa S, Kobayashi Y, Kawata E, Tajika K, Gomi S, Kanda J, Kobayashi A, Omori I, Marumo A, Fujiwara Y, Yui S, Terada K, Fukunaga K, Hirakawa T, Arai K, Kitano T, Kosaka F, Tamai H, Nakayama K, Wakita S, Fukuda T, Inokuchi K. Clinical characteristics and prognosis of acute myeloid leukemia associated with DNA-methylation regulatory gene mutations. Haematologica, 11時10分74-1081, 2016

20.Murayama T, Fukuda T, Okumura H, Sunami K, Sawazaki A, Maeda Y, Tsurumi H, Uike N, Hidaka T, Takatsuka Y, Eto T, Tsuda H, Fujisaki T, Miyamoto T, Tsuneyoshi N, Iyama S, Nagafuji K, Harada M. Efficacy of upfront high-dose chemotherapy plus rituximab followed by autologous peripheral blood stem cell transplantation for untreated high-intermediate-, and high-risk diffuse large B-cell lymphoma: a multicenter prospective phase II study (JSCT-NHL04). Int J Hematol, 103:676-685, 2016

21.Yakushijin K, Atsuta Y, Doki N, Yokota A, Kanamori H, Miyamoto T, Ohwada C, Miyamura K, Nawa Y, Kurokawa M, Mizuno I, Mori T, Onizuka M, Taguchi J, Ichinohe T, Yabe H, Morishima Y, Kato K, Suzuki R, Fukuda T. Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes. Bone Marrow Transplant, 51:403-409, 2016

22.Kato M, Yamashita T, Suzuki R, Matsumoto K, Nishimori H, Takahashi S, Iwato K, Nakaseko C, Kondo T, Imada K, Kimura F, Ichinohe T, Hashii Y, Kato K, Atsuta Y, Taniguchi S, Fukuda T. Donor cell-derived hematological malignancy: a survey by the Japan Society for Hematopoietic Cell Transplantation. Leukemia, 30:1742-1745, 2016

23.Asano T, Matsuoka K, Iyama S, Ohashi K, Inamoto Y, Ohwada C, Murata M, Satake A, Yoshida C, Nakase K, Mori Y, Tanimoto M. Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease. Acta Med Okayama, 70:429-433, 2016

24.Maeda Y, Nishimori H, Inamoto Y, Nakamae H, Sawa M, Mori Y, Ohashi K, Fujiwara S, Tanimoto M. An Open-labeled, Multicenter Phase II Study of Tamibarotene in Patients with Steroid-refractory Chronic Graft-versus-Host Disease. Acta Med Okayama, 70:409-412, 2016

25.Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, Arat M, Bader P, Baron F, Bazarbachi A, Blaise D, Ciceri F, Corbacioglu S, Dalle JH, Dignan F, Fukuda T, Huynh A, Masszi T, Michallet M, Nagler A, NiChonghaile M, Okamoto S, Pagliuca A, Peters C, Petersen FB, Richardson PG, Ruutu T, Savani BN, Wallhult E, Yakoub-Agha I, Duarte RF, Carreras E. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant, 51:906-912, 2016

26.Umemura K, Iwaki T, Kimura T, Ogawa C, Fukuda T, Taniguchi S, Horibe K, Goto H, Yoshimura K, Watanabe Y, Nitani C, Kikuta A. Pharmacokinetics and Safety of Defibrotide in Healthy Japanese Subjects. Clin Pharmacol Drug Dev, 5時54分8-551, 2016

27.Kohno S, Tamura K, Niki Y, Izumikawa K, Oka S, Ogawa K, Kadota J, Kamei K, Kanda Y, Kiuchi T, Shibuya K, Takakura S, Takata T, Takesue Y, Teruya K, Tokimatsu I, Fukuda T, Maesaki S, Makimura K, Mikamo H, Mitsutake K, Miyazaki Y, Mori M, Yasuoka A, Yano K, Yamanaka N, Yoshida M. Executive Summary of Japanese Domestic Guidelines for Management of Deep-seated Mycosis 2014. Med Mycol J, 57:E117-E163, 2016

28.Tada K, Maeshima AM, Hiraoka N, Yamauchi N, Maruyama D, Kim S-W, Watanabe T, Katayama N, Heike Y, Tobinai K, Kobayashi Y. Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy. Cancer Immunol Immunother, 65:1213-1222, 2016

29.Fukushima R, Kobayashi Y, Fukuhara S, Miyamoto Ki, Munakata W, Maruyama D, Kim S-W, Watanabe T, Taniguchi H, Maeshima A, Tobinai K. A retrospective analysis of combination chemotherapy consisting cyclophosphamide, vincristine, prednisolone and procarbazine (C-MOPP) for pretreated aggressive non-Hodgkin lymphoma. J Chemother, 28:116-122, 2016

30.Mitsuhashi K, Kako S, Shigematsu A, Atsuta Y, Doki N, Fukuda T, Kanamori H, Onizuka M, Takahashi S, Ozawa Y, Kurokawa M, Inoue Y, Nagamura-Inoue T, Morishima Y, Mizuta S, Tanaka J. Comparison of Cyclophosphamide Combined with Total Body Irradiation, Oral Busulfan, or Intravenous Busulfan for Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Lymphoblastic Leukemia. Biol Blood Marrow Transplant, 22時21分94-2200, 2016

31.Atsuta Y, Hirakawa A, Nakasone H, Kurosawa S, Oshima K, Sakai R, Ohashi K, Takahashi S, Mori T, Ozawa Y, Fukuda T, Kanamori H, Morishima Y, Kato K, Yabe H, Sakamaki H, Taniguchi S, Yamashita T. Late Mortality and Causes of Death among Long-Term Survivors after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant, 22時17分02-1709, 2016

32.Kanda J, Ikegame K, Fuji S, Kurokawa M, Kanamori H, Fukuda T, Ohashi K, Ishikawa J, Ogawa H, Inoue M, Ichinohe T, Atsuta Y, Kanda Y. Haploidentical and Matched Sibling Donor Hematopoietic Cell Transplantation for Patients with HLA-Homozygous Haplotypes. Biol Blood Marrow Transplant, 22時20分31-2037, 2016

33.Uchino K, Mizuno S, Mizutani M, Horio T, Hanamura I, Espinoza JL, Matsuo K, Onizuka M, Kashiwase K, Morishima Y, Fukuda T, Kodera Y, Doki N, Miyamura K, Mori TMT, Takami A. Toll-like receptor 1 variation increases the risk of transplant-related mortality in hematologic malignancies. Transpl Immunol, 38:60-66, 2016

34.Ishiyama K, Yamaguchi T, Eto T, Ohashi K, Uchida N, Kanamori H, Fukuda T, Miyamura K, Inoue Y, Taguchi J, Mori T, Iwato K, Morishima Y, Nagamura-Inoue T, Atsuta Y, Sakamaki H, Takami A. Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT. Leuk Res, 47:47-53, 2016

35.Kawamura K, Ikeda T, Hagiwara S, Mori T, Shinagawa A, Nishiwaki K, Ohashi K, Kubonishi S, Fukuda T, Ito T, Tomita N, Ichinohe T, Kato K, Morishima Y, Atsuta Y, Sunami K, Kanda Y. Tandem autologous versus autologous/allogeneic transplantation for multiple myeloma: propensity score analysis. Leuk Lymphoma, 57:2077-2083, 2016

36.Arai Y, Kondo T, Yamazaki H, Takenaka K, Sugita J, Kobayashi T, Ozawa Y, Uchida N, Iwato K, Kobayashi N, Takahashi Y, Ishiyama K, Fukuda T, Ichinohe T, Atsuta Y, Mori T, Teshima T. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia. Haematologica, 101:644-652, 2016

37.Mizutani M, Hara M, Fujita H, Aoki J, Kanamori H, Ohashi K, Usuki K, Fukuda T, Chou T, Tanaka J, Atsuta Y, Takami A. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR. Bone Marrow Transplant, 51:645-653, 2016

38.Mori J, Ishiyama K, Yamaguchi T, Tanaka J, Uchida N, Kobayashi T, Fukuda T, Kanamori H, Miyamura K, Takahashi S, Eto T, Hirokawa M, Mori S, Nagamura T, Atsuta Y, Takami A. Outcomes of allogeneic hematopoietic cell transplantation in patients with biphenotypic acute leukemia. Ann Hematol, 95:295-300, 2016

39.Yanada M, Kanda J, Ohtake S, Fukuda T, Sakamaki H, Miyamura K, Miyawaki S, Uchida N, Maeda T, Nagamura-Inoue T, Asou N, Morishima Y, Atsuta Y, Miyazaki Y, Kimura F, Kobayashi Y, Takami A, Naoe T, Kanda Y. Unrelated bone marrow transplantation or immediate umbilical cord blood transplantation for patients with acute myeloid leukemia in first complete remission. Eur J Haematol, 97:278-287, 2016

40.Kanda J, Brazauskas R, Hu Z-H, Kuwatsuka Y, Nagafuji K, Kanamori H, Kanda Y, Miyamura K, Murata M, Fukuda T, Sakamaki H, Kimura F, Seo S, Aljurf M, Yoshimi A, Milone G, Wood WA, Ustun C, Hashimi S, Pasquini M, Bonfim C, Dalal J, Hahn T, Atsuta Y, Saber W. Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations. Biol Blood Marrow Transplant, 22:744-751, 2016

41.Aoki J, Seo S, Kanamori H, Tanaka M, Fukuda T, Onizuka M, Kobayashi N, Kondo T, Sawa M, Uchida N, Iwato K, Icihnohe T, Atsuta Y, Yano S, Takami A. Impact of low-dose TBI on outcomes of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for AML. Bone Marrow Transplant, 51:604-606, 2016

42.Sakai R, Taguri M, Oshima K, Mori T, Ago H, Adachi S, Morita S, Taniguchi S, Fukuda T, Ohashi K, Eto T, Miyamura K, Iwato K, Kobayashi N, Kanamori H, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Murata M. A comparison of tacrolimus and cyclosporine combined with methotrexate for graft-versus-host disease prophylaxis, stratified by stem cell source: a retrospective nationwide survey. Int J Hematol, 13時32分2-333, 2016

43.Itonaga H, Iwanaga M, Aoki K, Aoki J, Ishiyama K, Ishikawa T, Sakura T, Fukuda T, Najima Y, Yujiri T, Mori T, Kurokawa M, Nawa Y, Uchida N, Morishita Y, Hashimoto H, Eto T, Hirokawa M, Morishima Y, Nagamura-Inoue T, Atsuta Y, Miyazaki Y. Impacts of graft-versus-host disease on outcomes after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: A nationwide retrospective study. Leuk Res, 41:48-55, 2016

44.Aoki J, Kanamori H, Tanaka M, Yamasaki S, Fukuda T, Ogawa H, Iwato K, Ohashi K, Okumura H, Onizuka M, Maesako Y, Teshima T, Kobayashi N, Morishima Y, Hirokawa M, Atsuta Y, Yano S, Takami A. Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia. Am J Hematol, 91:302-307, 2016

45.Arima N, Nakamura F, Yabe T, Tanaka J, Fuji S, Ohashi K, Fukuda T, Miyamura K, Iwato K, Eto T, Mori T, Kobayashi N, Hoshino T, Kato C, Kanamori H, Nakamae H, Atsuta Y, Morishima Y, Kanda Y. Influence of Differently Licensed KIR2DL1-Positive Natural Killer Cells in Transplant Recipients with Acute Leukemia: A Japanese National Registry Study. Biol Blood Marrow Transplant, 22時42分3-431, 2016

46.Nishiwaki S, Imai K, Mizuta S, Kanamori H, Ohashi K, Fukuda T, Onishi Y, Takahashi S, Uchida N, Eto T, Nakamae H, Yujiri T, Mori S, Nagamura-Inoue T, Suzuki R, Atsuta Y, Tanaka J. Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT. Bone Marrow Transplant, 51:43-50, 2016

47.Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, Najima Y, Fukuda T, Uchida N, Takahashi S, Nagamura-Inoue T, Morishima Y, Miyamura K. Comparison of Outcomes of 08月08日 and 07月08日 Allele-Matched Unrelated Bone Marrow Transplantation and Single-Unit Cord Blood Transplantation in Adults with Acute Leukemia. Biol Blood Marrow Transplant, 22時33分0-338, 2016

48.Arai Y, Kanda J, Nakasone H, Kondo T, Uchida N, Fukuda T, Ohashi K, Kaida K, Iwato K, Eto T, Kanda Y, Nakamae H, Nagamura-Inoue T, Morishima Y, Hirokawa M, Atsuta Y, Murata M. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant, 51:96-102, 2016