Treatment of refractory CMV-infection following hematopoietic stem cell transplantation with the combination of foscarnet and leflunomide

Background: Treatment of cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation (HSCT) is limited by toxicities of current antiviral drugs and the occurrence of drug resistant strains. Leflunomide, an immunosuppressive agent used for treatment of rheumatoid arthritis, also has activity against CMV by impairing viral assembly. Here we report the control of refractory CMV disease by the combined use of foscarnet and leflunomide. Patients and results: A 1 1/2-year-old boy with juvenile myelo-monocytic leukemia (JMML) received an allogeneic HSCT with bone marrow stem cells from a mismatched, unrelated donor (MMUD, recipient and donor CMV-positive). CMV-reactivation two months post transplantation (Tx) could only be controlled by the use of cidofovir. Because of secondary graft failure, the boy received a second HSCT with peripheral blood stem cells (PBSC) of the same donor after overall 6 months. CMV-infection was noticed three weeks later, associated with a considerable rise of both CMV-copy number and pp65-antigen. Since reinduction with cidofovir was ineffective and ganciclovir not warranted due to the history of graft failure, the child then received a combination of foscarnet/leflunomide, leading to a rapid decline of his CMV-copy number and to an afebrile state. Hematological, hepatic or renal toxicities were not observed. Conclusion: This case report suggests that leflunomide may be of use in the management of transplant recipients with CMV-infection refractory or intolerant to conventional antiviral therapy.