Leflunomide as a rescue treatment in ganciclovir-resistant cytomegalovirus infection in a seronegative renal transplant recipient--a case report.
BACKGROUND
Cytomegalovirus (CMV) infection is a frequent complication of immunosuppressive treatment after solid organ and bone marrow transplantation. Prophylaxis and treatment with ganciclovir is successful in most cases, but frequency of infections with ganciclovir-resistant CMV mutants has grown in recent years. Leflunomide, an immunosuppressive drug used in rheumatic diseases and which also exerts antiviral activity, could be a useful treatment option in such cases.


METHODS
A 60-year-old, CMV-seronegative patient received a kidney graft from a CMV-seropositive donor. The post-transplant period was complicated by 2 episodes of biopsy-proven graft rejection treated with steroid pulses. CMV viremia was diagnosed 4 weeks after transplantation. The patient received treatment with intravenous ganciclovir and anti-CMV immunoglobulins with consecutive oral valganciclovir therapy. He was admitted to our hospital 6 months after transplantation, with symptoms of CMV infection confirmed by high viral load in his blood. Treatment with double-dose ganciclovir and anti-CMV immunoglobulins did not decrease CMV viremia, so we diagnosed ganciclovir-resistant CMV infection. We decided to discontinue mycophenolic acid treatment and start leflunomide 20 mg BID. This therapy led to rapid decrease and final disappearance of CMV viremia. Kidney graft function remained stable during leflunomide treatment. Seroconversion in both IgM and IgG anti-CMV classes was observed.


CONCLUSIONS
Treatment with leflunomide is a reasonable option in ganciclovir-resistant infection in kidney transplant recipients, providing effective viral elimination and reconstitution of adaptive anti-CMV immunity without excess risk of graft rejection.
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Michał
M
Ciszek
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Krzysztof
K
Mucha
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Bartosz
B
Foroncewicz
Department of General and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland.
Andrzej
A
Chmura
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Leszek
L
Pączek
D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000276:immunology; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D016867:Immunocompromised Host; D007136:Immunoglobulins / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous; D007555:Isoxazoles / Q000627:therapeutic use*; D016030:Kidney Transplantation; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007555:Isoxazoles; C045781:cytomegalovirus-specific hyperimmune globulin; D000077339:Leflunomide; D015774:Ganciclovir