Use of foscarnet for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation from a related donor

Abstract

Foscarnet is an active agent against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT), as well as ganciclovir. We investigated the usefulness of foscarnet in patients who underwent related allogeneic HSCT. Foscarnet was used in 320 patients with a median age of 45 years (range 15-72). The purpose of administration was CMV disease in 65, preemptive use in 248 and prophylaxis in 7. Totally, 194 patients had a history of prior ganciclovir treatment. The reason for foscarnet use was insufficient therapeutic effect of prior ganciclovir in 99, and adverse event including myelosuppression in 95. The response rate in symptom was 52% for the CMV disease patients. Antigenemia disappeared in 77% of the preemptive treatment and improved in 13% of the patients. No outbreak of CMV disease was recognized. The total effectiveness of therapeutic and preemptive use was significantly higher for patients without prior ganciclovir (91 vs. 76%, P = 0.001). Adverse events of grade 3 or higher were recognized in 24%, including electrolyte abnormalities in 11%, neutropenia in 8%, and thrombocytopenia in 8%. Renal damage was only observed in 3% of patients. Foscarnet was concluded to be a safe and effective anti-CMV agent and to be a suitable alternative to ganciclovir.

UL54 foscarnet mutation in an hematopoietic stem cell transplant recipient with cytomegalovirus disease

“…However, published studies of FOS therapy for CMV indicate that resistance has not been described, even at doses lower than the dose our patient received. In 313 HSCT recipients with CMV antigenemia or disease who received FOS for therapy, the median initial FOS dose was 88 mg/kg twice daily and no resistance was reported . Also, no FOS resistance was noted in 110 HSCT recipients with CMV antigenemia treated with FOS 60–90 mg/kg twice daily for 14–28 days , making it unclear if profound immunosuppression or the duration and intensity of FOS exposure played a more significant role in the development of resistance in our patient.…”

“…The rarity of isolated FOS mutations is, in part, a result of the typical practice of VGCV use preceding the use of FOS. In HSCT recipients, however, the myelosuppressive toxicity of GCV leads to initial use of FOS more commonly than in other populations . Despite this practice, the initial detection of UL54 FOS resistance alone, without UL97 mutations, is rarely reported.…”

Safety profile of the concomitant use of foscarnet and aerosolized pentamidine in allogeneic hematopoietic stem cell transplantation recipients

“…On the other hand, the previous study reported that grade 3/4 electrolyte abnormalities and renal damage associated with foscarnet occurred in 10.9% and 3.4% of the patients. 24 Although considering slight differences in evaluation methods for adverse effects, there appeared no remarkable difference between both results. Therefore, the safety of concomitant use of aerosolized pentamidine in this study was considered to be similar to that of foscarnet monotherapy.…”

“…The present study showed that the incidences of grade 3/4 hypocalcemia, hypomagnesemia, and creatinine increase were 9.1%, 6.4%, and 3.6%, respectively, in the non‐pentamidine group. On the other hand, the previous study reported that grade 3/4 electrolyte abnormalities and renal damage associated with foscarnet occurred in 10.9% and 3.4% of the patients . Although considering slight differences in evaluation methods for adverse effects, there appeared no remarkable difference between both results.…”

Management of cytomegalovirus infection in haemopoietic stem cell transplantation

“…Further evidence of foscarnet efficacy comes from case series. In one, 313 patients were treated for CMV disease ( n = 65), or were given pre‐emptive therapy of CMV reactivation in related‐ donor transplants ( n = 248) (Asakura et al , ). Of 194 patients had failed previous ganciclovir due to lack of efficacy ( n = 99) or myelosuppression in ( n = 95).…”