Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections

Abstract

Summary:Pre-emptive antiviral therapy for CMV infection following allogeneic stem cell transplantation is an effective strategy for preventing CMV disease. This entails the logistic difficulty of daily intravenous therapy with ganciclovir or foscarnet to clinically asymtomatic patients. Cidofovir (CDV) is effective against CMV in vitro and has the practical advantage of weekly administration. However, there are limited data on the pre-emptive use of CDV in CMV infections. We carried out a pilot study exploring the efficacy and toxicity of CDV as primary pre-emptive therapy for CMV infections monitored by PCR-based assays. CDV was used at 5 mg/kg with probenecid and hydration, weekly for a maximum of 4 weeks, followed by fortnightly maintenance treatment. Four patients were treated with CDV and two of them responded. Both the non-responders developed CMV disease. There was no renal toxicity noted in any of the patients, but three patients had severe vomiting and one developed uveitis, which precluded maintenance treatment in the two responders. Following failure of CDV, foscarnet was effective in controlling the CMV infection in both patients, although the infection recurred in both. Thus, larger randomised studies are required before CDV can be recommended as a primary pre-emptive therapy for post-transplant CMV infections. Bone Marrow Transplantation (2001) 28, 879-881.

Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation

“…Little experience has been accumulated so far with the use of CDV for CMV reactivation after pediatric allo-SCT, since most of data available concerns adult patients (Chakrabarti et al, 2001;Ljungman et al, 2001;Platzbacker et al, 2001).…”

“…CDV was given 5 mg/(kg week) twice (induction), followed by a maintenance of two to four fortnightly doses at 3-5 mg/kg, as reported previously by others (Bosi et al, 2002;Chakrabarti et al, 2001). As prophylaxis for CDV nephrotoxicity, the following measures were adopted: intravenous hydration with normal saline; administration of oral probenecid (25-30 mg/kg (maximum 2 g) 3 h before CDV; 10-15 mg/kg (maximum 1 g) 2 and 8 h after CDV); and monitoring of renal function, proteinuria and electrolyte abnormalities before CDV administration and within a week of its withdrawal.…”

Prevention and Treatment of Cancer-Related Infections

“…152,153,165,166 In a retrospective study in allogeneic HSCT recipients (N=82) that evaluated cidofovir for treatment of CMV disease (n=20), primary preemptive therapy (n=24), or secondary preemptive therapy (n=38), response was observed in 50% of patients treated for CMV disease (mainly CMV pneumonia) and 62% treated for primary preemptive therapy. 152 Moreover, secondary preemptive therapy with cidofovir resulted in response in 66% of patients who had experienced either failure or relapse (defined as continued presence or recurrence of pp65 antigenemia or viral DNA after at least 1 week of antivirals) after initial preemptive therapy with ganciclovir, foscarnet, or the combination of these agents.…”

Immunocompromised Hosts: Perspectives in the Treatment and Prophylaxis of Cytomegalovirus Disease in Solid‐Organ Transplant Recipients

“…However, limited data are available on its use in SOT recipients [10]. Findings of a retrospective study of 82 allogeneic stem cell transplant recipients suggest that cidofovir may be used for secondary preemptive therapy in patients with relapsed CMV infection and in treatment of CMV disease in patients who experienced failure of ganciclovir or foscarnet therapy [24,25]. No data from randomized, clinical trials are available to support the use of cidofovir in SOT recipients.…”