Foscarnet in the management of cytomegalovirus infections in hematopoietic stem cell transplant patients

Abstract

Despite significant advances in the day-to-day management of patients receiving hematopoietic stem cell transplantations, including the introduction of new antiviral drugs, cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality. The aim of this article is to undertake a literature-based review of foscarnet in this therapeutic setting and to align current best-published evidence with recent recommendations presented at the European Conference on Infections in Leukaemia. Ganciclovir remains the mainstay of CMV infection/disease antiviral management protocols. However, approximately a third of patients develop severe neutropenia and others become resistant to ganciclovir, and thus, a reasonably large proportion of patients are not able to receive and/or continue with this medication. Foscarnet is a suitable option as both pre-emptive therapy or for the treatment of active disease in these patients. Randomized trials have demonstrated that foscarnet is equally effective when compared with ganciclovir for pre-emptive treatment of CMV infections: the outcome was comparable with ganciclovir in terms of control of antigenemia and survival rates. There is a paucity of information for its use in the prophylaxis of CMV, although preliminary data show that it was effective in some patients at high risk of CMV reactivation. The main adverse events associated with foscarnet are renal impairment, serum electrolyte and hemoglobin disturbances, seizures and local genital irritation/ulceration. Foscarnet is a well-established antiviral option in immunocompromised patients, and it is usually administered as a second-line option to ganciclovir. In patients receiving hematopoietic stem cell transplantation, it has proven efficacy when used pre-emptively to treat CMV reactivation, as an alternative to and also in combination with ganciclovir.

Outcomes in Transplant Recipients Treated With Foscarnet for Ganciclovir-Resistant or Refractory Cytomegalovirus Infection

“…A review by Bacigalupo et al 16 summarizes those evaluating the use of foscarnet for prophylaxis and preemptive therapy as well as for treatment. Studies in the last 15 years that included at least 6 transplant recipients who were treated with foscarnet for established CMV infection, and that reported mortality outcomes, are summarized in Table 4.…”

“…Mortality data estimated from Fig 5B, p. 356 16 . Renal dysfunction data refers to the entire group which included those receiving FOS for preemptive therapy 16 . ** Although overall nephrotoxicity was not reported in Isada et al, 4 of 5 (80%) of kidney transplant recipients developed graft loss 2 . Abbreviations: GCV-R – ganciclovir-resistant; SOT – solid organ transplant; HCT – hematopoietic cell transplant; FOS – foscarnet; R/R – resistant/refractory; NR – not reported. …”

“…Mortality data estimated from Fig 5B, p. 356 16 . Renal dysfunction data refers to the entire group which included those receiving FOS for preemptive therapy 16 . …”

“…Despite an extensive literature on CMV in transplantation, only a few studies in the last 15 years have described foscarnet treatment outcomes outside of preemptive therapy 16–23 . Here, outcomes were reviewed from SOT and HCT recipients who had received foscarnet for treatment of resistant or refractory CMV over a 10-year period at a single center.…”

Quiescent Crohn’s Disease in Clinical Remission With 6-Mercaptopurine: A Breeding Ground for CMV Pneumonia as Part of a Viral Infection Domino

“…The above clinical, laboratory and radiologic findings were strongly suggestive of CMV pneumonitis; thus, intravenous foscarnet (6 g bid/d) was initiated. Foscarnet was selected over ganciclovir, due to existing pancytopenia and effectiveness against possible resistant CMV strains [8]. Therapy to cover for atypical pneumonia was continued until a definitive diagnosis could be reached.…”