Leflunomide failure to control recurrent cytomegalovirus infection in the setting of renal failure after allogeneic stem cell transplantation

Abstract

Cytomegalovirus (CMV) reactivation is common in the allogeneic stem cell transplant setting but the incidence of CMV organ disease and mortality has been dramatically reduced by prophylactic or preemptive antiviral therapy. We report the case of a CMV-seropositive 46-year-old man with non-Hodgkin's lymphoma who underwent an unrelated allogeneic stem cell transplant from a CMV-seronegative HLA-matched unrelated donor. CMV encephalitis and colitis developed that was refractory to single-agent therapy. The CMV isolate demonstrated genotypic resistance to both ganciclovir and foscarnet. CMV disease was controlled by prolonged combination ganciclovir and cidofovir therapy, but severe renal dysfunction developed. Leflunomide was selected as a last resort to avoid the nephrotoxicity of cidofovir. CMV antigenemia rapidly increased following leflunomide administration, necessitating discontinuing this agent and resuming prior antiviral therapy. The pharmacokinetics of leflunomide in the setting of renal insufficiency is presented. Options for salvage therapy in refractory CMV disease in allogeneic stem cell transplant recipients are briefly reviewed.

Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV)

“…There are also reports of efficacy studies in animal models with banzi virus, influenza B virus, and vaccinia virus (36) that showed either a lack of or very limited efficacy. Clinical trials in humans were also reported for HIV, CMV, and BK virus (38,(40)(41)(42)(43), with no conclusive results. It is reported that mean levels of circulating uridine in man are approximately 6 μM (44), spanning a range between 2.6 μM (45) and 21 μM (46).…”

CMV: Prevention, Diagnosis and Therapy

“…The antimalarial artesunate (127) has anti-CMV effects that may be clinically helpful, especially with resistant disease (128). Leflunomide (am immunosuppressive agent approved for rheumatoid arthritis) has antiviral activity and has been reported to clear CMV viremia in transplant recipients with resistant CMV (129-132), but failure has been reported (133).…”

CMV central nervous system disease in stem-cell transplant recipients: an increasing complication of drug-resistant CMV infection and protracted immunodeficiency

“…This review yielded nine cases of CMV CNS disease in SCT recipients, which meet the criteria for CMV disease of the CNS. [4][5][6][7][8][9][10][11][12] Data from these nine cases along with the two UCLA cases (a total of 11 patients) are summarized in Table 1. Except for one pediatric patient, all patients were adults (median age, 46 years).…”