title: 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.
abstract: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT.
  
  
  
  We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT.
  
  
  
  Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome.
  
  
  
  Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan. sfuji@ncc.go.jp.
authors: Shigeo
authors: S
authors: Fuji
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yoshitaka
authors: Y
authors: Inoue
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Atae
authors: A
authors: Utsunomiya
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yukiyoshi
authors: Y
authors: Moriuchi
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Kaoru
authors: K
authors: Uchimaru
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Ilseung
authors: I
authors: Choi
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Eiichi
authors: E
authors: Otsuka
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Hideho
authors: H
authors: Henzan
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Koji
authors: K
authors: Kato
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takeaki
authors: T
authors: Tomoyose
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Hisashi
authors: H
authors: Yamamoto
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Saiko
authors: S
authors: Kurosawa
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Ken-Ichi
authors: K
authors: Matsuoka
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takuhiro
authors: T
authors: Yamaguchi
authors: Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takahiro
authors: T
authors: Fukuda
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; C549035:mogamulizumab