title: Acyclovir-resistant herpes simplex virus 1 infection early after allogeneic hematopoietic stem cell transplantation with T-cell depletion.
abstract: We previously reported that oral low-dose acyclovir (200 mg/day) for the prevention of herpes simplex virus (HSV) infections after allogenic hematopoietic stem cell transplantation (HSCT) is effective without the emergence of acyclovir-resistant HSV infections. However, HSV infections are of significant concern because the number of allogeneic HSCT with T-cell depletion, which is a risk factor of the emergence of drug-resistant HSV infections, has been increasing. We experienced a 25-year-old female who received allogenic HSCT from an unrelated donor with 1-antigen mismatch using anti-thymocyte globulin. Despite acyclovir prophylaxis (200 mg/day), she developed the right palatal ulcer that was positive for HSV-1 specific antigen by fluorescent antibody on day 20 and developed new hypoglossal and tongue ulcers on day 33. Replacement of acyclovir with foscarnet improved her ulcers. We isolated 2 acyclovir-resistant and foscarnet-sensitive strains from the right palatal and hypoglossal ulcers, which had the same frame shift mutation in the thymidine kinase genes. The rate of proliferation of the isolate from the hypoglossal ulcer was faster than that from the right palatal ulcer in the plaque reduction assay. HSV strains that acquired acyclovir-resistant mutations at the right palatal ulcer with larger plaque might spread to the hypoglossal ulcer as the secondary site of infection because of better growth property. Second-line antiviral agents should be considered when we suspect treatment failure of HSV infection, especially in HSCT with T-cell depletion. Further studies are required whether low-dose acyclovir prophylaxis leads to the emergence of virological resistance.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Akahoshi
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Department of Virology, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Ohno
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Komiya
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Gomyo
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Hayakawa
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Naonori
authors.initials: N
authors.lastname: Harada
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kameda
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Ugai
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Kiriko
authors.initials: K
authors.lastname: Terasako-Saito
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Shun-Ichi
authors.initials: SI
authors.lastname: Kimura
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kako
authors.affiliation: Department of Virology, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Kimiyasu
authors.initials: K
authors.lastname: Shiraki
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma, Omiya-ku, Saitama, Saitama 330-8503, Japan. Electronic address: ycanda-tky@umin.ac.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006561:Herpes Simplex / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D013601:T-Lymphocytes / Q000276:immunology; D014059:Tongue / Q000473:pathology; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir
keywords: Allogeneic hematopoietic stem cell transplantation; Herpes simplex virus; In vivo T-cell depletion; Virological resistance