Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients

A Prospective Multicenter Trial with an Historical Control Group

Masao Ogata, Kuniko Takano, Yukiyoshi Moriuchi, Tadakazu Kondo, Toshimitsu Ueki, Nobuaki Nakano, Takehiko Mori, Nobuhiko Uoshima, Koji Nagafuji, Satoshi Yamasaki, Yasuhiko Shibasaki, Rika Sakai, Koji Kato, Ilseung Choi, Yumi Jo, Tetsuya Eto, Shinichi Kako, Kumi Oshima, Takahiro Fukuda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 104 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P <.001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P =.14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P =.96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD.

Original languageEnglish
JournalBiology of Blood and Marrow Transplantation
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Foscarnet
Human Herpesvirus 6
Fetal Blood
Multicenter Studies
Transplantation
Graft vs Host Disease
Control Groups
Incidence
Therapeutics
Human Herpesvirus 6 encephalitis
Transplant Recipients
Multivariate Analysis
DNA

Keywords

  • Acute GVHD
  • Foscarnet
  • HHV-6 encephalitis
  • Human herpesvirus-6
  • Prophylaxis

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients : A Prospective Multicenter Trial with an Historical Control Group. / Ogata, Masao; Takano, Kuniko; Moriuchi, Yukiyoshi; Kondo, Tadakazu; Ueki, Toshimitsu; Nakano, Nobuaki; Mori, Takehiko; Uoshima, Nobuhiko; Nagafuji, Koji; Yamasaki, Satoshi; Shibasaki, Yasuhiko; Sakai, Rika; Kato, Koji; Choi, Ilseung; Jo, Yumi; Eto, Tetsuya; Kako, Shinichi; Oshima, Kumi; Fukuda, Takahiro.

In: Biology of Blood and Marrow Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Ogata, M, Takano, K, Moriuchi, Y, Kondo, T, Ueki, T, Nakano, N, Mori, T, Uoshima, N, Nagafuji, K, Yamasaki, S, Shibasaki, Y, Sakai, R, Kato, K, Choi, I, Jo, Y, Eto, T, Kako, S, Oshima, K & Fukuda, T 2018, 'Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial with an Historical Control Group', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2018.02.008
Ogata, Masao ; Takano, Kuniko ; Moriuchi, Yukiyoshi ; Kondo, Tadakazu ; Ueki, Toshimitsu ; Nakano, Nobuaki ; Mori, Takehiko ; Uoshima, Nobuhiko ; Nagafuji, Koji ; Yamasaki, Satoshi ; Shibasaki, Yasuhiko ; Sakai, Rika ; Kato, Koji ; Choi, Ilseung ; Jo, Yumi ; Eto, Tetsuya ; Kako, Shinichi ; Oshima, Kumi ; Fukuda, Takahiro. / Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients : A Prospective Multicenter Trial with an Historical Control Group. In: Biology of Blood and Marrow Transplantation. 2018.
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abstract = "Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 104 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3{\%} versus 57.3{\%}, P <.001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4{\%}; standard-treatment group, 4.9{\%}; P =.14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0{\%}; standard-treatment group, 40.5{\%}; P =.96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5{\%}; standard-treatment group, 14.5{\%}; P = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD.",
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T2 - A Prospective Multicenter Trial with an Historical Control Group

AU - Ogata, Masao

AU - Takano, Kuniko

AU - Moriuchi, Yukiyoshi

AU - Kondo, Tadakazu

AU - Ueki, Toshimitsu

AU - Nakano, Nobuaki

AU - Mori, Takehiko

AU - Uoshima, Nobuhiko

AU - Nagafuji, Koji

AU - Yamasaki, Satoshi

AU - Shibasaki, Yasuhiko

AU - Sakai, Rika

AU - Kato, Koji

AU - Choi, Ilseung

AU - Jo, Yumi

AU - Eto, Tetsuya

AU - Kako, Shinichi

AU - Oshima, Kumi

AU - Fukuda, Takahiro

PY - 2018/1/1

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N2 - Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 104 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P <.001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P =.14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P =.96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD.

AB - Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 104 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P <.001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P =.14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P =.96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD.

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KW - Human herpesvirus-6

KW - Prophylaxis

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