Occurrence of adverse events caused by valganciclovir as pre-emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low-dose administration.
BACKGROUND
Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported.


METHODS
We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed.


RESULTS
Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04).


CONCLUSIONS
Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.
Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
M
M
Takahata
Health Care Center, Hokkaido University, Sapporo, Japan.
S
S
Hashino
Department of Hematology, NTT Higashinihon Sapporo Hospital, Sapporo, Japan.
M
M
Nishio
Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
J
J
Sugita
Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
A
A
Shigematsu
Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
M
M
Onozawa
Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
K
K
Fujimoto
Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
T
T
Endo
Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
T
T
Kondo
Department of Hematology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
J
J
Tanaka
Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
M
M
Imamura
Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
T
T
Teshima
D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced; D000077562:Valganciclovir
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir
CMV; VGCV; adverse events; low-dose administration; pre-emptive therapy