IMPACT OF LONG-TERM ACYCLOVIR ON CYTOMEGALOVIRUS-INFECTION AND SURVIVAL AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Cytomegalovirus (CMV) infection is a major cause of morbidity and mort ality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir gi ven around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double- dummy design: intravenous acyclovir (500 mg/m(2), three times a day) f or 1 month followed by oral acyclovir (800 mg four times a day for a f urther 6 months) (intravenous/oral group); intravenous acyclovir follo wed by oral placebo (intermediate group); or low-dose oral acyclovir ( 200 or 400 mg, four times a day) followed by placebo (''controls''). A nalysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. Th ere was no further reduction in infection risk with the addition of lo ng-term oral acyclovir. Time to CMV viraemia was delayed in the intrav enous/oral acyclovir group compared with controls. Extending the proph ylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 contro ls (p=0.012). Although the intravenous/oral acyclovir group did signif icantly better than controls in terms of survival, the difference betw een the intravenous/oral acyclovir group and the intermediate group wa s of borderline statistical significance (p=0.054). Adverse events tha t were possibly treatment related were similar in all three groups. Th e most commonly reported events were nausea, vomiting, elevated creati nine, and renal failure.