Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial.
OBJECTIVE
To evaluate the efficacy and safety of ganciclovir for prevention of cytomegalovirus (CMV) infection and disease.


METHODS
A randomized, placebo-controlled, double-blind trial.


METHODS
University-affiliated bone marrow transplant center.


METHODS
Cytomegalovirus-seropositive allogeneic bone marrow transplant recipients.


METHODS
Random assignment to receive either a placebo or ganciclovir at a dose of 2.5 mg/kg body weight every 8 hours for 1 week before transplant and then at a dose of 6 mg/kg once per day, Monday through Friday, after transplant when the post-transplant neutrophil count reached 1.0 x 10(9)/L.


METHODS
Cytomegalovirus infection (positive culture, seroconversion, positive histologic findings), CMV disease (pneumonia, gastroenteritis, the wasting syndrome), and study-drug toxicity.


RESULTS
Cytomegalovirus infection developed in 25 of 45 placebo patients (56%) but in only 8 of 40 ganciclovir patients (20%) (P < 0.001). Cytomegalovirus disease may also have occurred less often in the ganciclovir patients (4 of 40 patients [10%] versus 11 of 45 patients [24%]; P = 0.09). The probability of CMV disease occurring within the first 120 days after transplantation was 0.29 among the placebo patients but only 0.12 among ganciclovir patients (P = 0.06). Reversible neutropenia was the only appreciable toxicity related to ganciclovir and required interruption of the study drug after transplant in 25 of 43 ganciclovir patients (58%) and in 13 of 47 placebo patients (28%) (P = 0.005). Overall survival was similar in both the placebo patients (29 of 45 [64%]) and ganciclovir patients (28 of 40 [70%]; P > 0.2).


CONCLUSIONS
Prophylactic ganciclovir, started before transplant and continued after recovery of the post-transplant neutrophil count, reduces the incidence and severity of CMV infection in CMV-sero-positive bone marrow transplant recipients but is frequently associated with neutropenia.
UCLA Center for the Health Sciences.
D J
DJ
Winston
W G
WG
Ho
K
K
Bartoni
C
C
Du Mond
D F
DF
Ebeling
W C
WC
Buhles
R E
RE
Champlin
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000401:mortality; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000627:therapeutic use*; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009894:Opportunistic Infections / Q000517:prevention & control*; D012698:Serologic Tests; D018139:Simplexvirus / Q000187:drug effects; D015996:Survival Rate; D017201:Virus Shedding / Q000187:drug effects
D015774:Ganciclovir