title: Response-oriented preemptive therapy against cytomegalovirus disease with low-dose ganciclovir: a prospective evaluation.
abstract: BACKGROUND
  Preemptive therapy against cytomegalovirus (CMV) disease has succeeded in reducing the incidence of CMV disease, but the toxicity of ganciclovir remains problematic.
  
  
  METHODS
  We prospectively evaluated the efficacy and toxicity of a preemptive protocol with ganciclovir at a reduced initial dose in 40 patients who achieved engraftment after allogeneic hematopoietic stem cell transplantation.
  
  
  RESULTS
  Twenty-three (58%) patients had high-risk features, including transplant from an HLA-mismatched or unrelated donor, or associated acute graft-versus-host disease. CMV antigenemia assay was performed weekly, and ganciclovir was started in a risk-adapted manner, in which the initial dose of ganciclovir was fixed at 5 mg/kg/d and then adjusted based on the results of a weekly CMV antigenemia assay. In this protocol, 23 (58%) patients demonstrated positive antigenemia, and 19 (48%) received a preemptive administration of ganciclovir. Only one patient had CMV disease in the gastrointestinal system, which was successfully treated with a regular therapeutic dose of ganciclovir. Consequently, the total dose of ganciclovir was significantly less than that in a previous protocol using the conventional double dose (5 mg/kg twice daily) of ganciclovir (134 mg/kg vs. 190 mg/kg on average, P=0.046). There were no significant toxicities attributed to ganciclovir, except for neutropenia <0.5 x 109/L, which developed in three patients for 3, 4, and 14 days, respectively, with granulocyte colony-stimulating factor support.
  
  
  CONCLUSIONS
  Preemptive therapy with a low initial dose of ganciclovir appeared to be effective even in high-risk patients. Further randomized controlled trial is warranted.
authors.affiliation: Stem Cell Transplant Unit, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.forename: Shin
authors.initials: S
authors.lastname: Mineishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Hironari
authors.initials: H
authors.lastname: Niiya
authors.forename: Aki
authors.initials: A
authors.lastname: Chizuka
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Nakai
authors.forename: Toshio
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Makimoto
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tanosaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D015774:Ganciclovir