title: Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease.
abstract: Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugio
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Electronic address: kojikato@intmed1.med.kyushu-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Hematology, Kitakyushu Municipal Medical Center, Fukuoka, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Saito
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Shuro
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawano
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Hideho
authors.initials: H
authors.lastname: Henzan
authors.affiliation: Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kadowaki
authors.affiliation: Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Takase
authors.affiliation: Department of Hematology, JCHO Kyushu Hospital, Fukuoka, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Muta
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Miyawaki
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamauchi
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shima
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Goichi
authors.initials: G
authors.lastname: Yoshimoto
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kamezaki
authors.affiliation: Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: Katsuto
authors.initials: K
authors.lastname: Takenaka
authors.affiliation: Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Department of Hematology, JCHO Kyushu Hospital, Fukuoka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Department of Hematology, Kitakyushu Municipal Medical Center, Fukuoka, Japan.
authors.forename: Yuju
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kamimura
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C549035:mogamulizumab
keywords: Adult T cell leukemia/lymphoma; Allogeneic hematopoietic stem cell transplantation; Graft-versus-host disease; Mogamulizumab