Ciszek Michał, Mucha Krzysztof, Foroncewicz Bartosz, Chmura Andrzej, Pączek Leszek
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Department of General and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland.
Ann Transplant. 2014 Jan 30;19:60-3. doi: 10.12659/AOT.884035.
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.
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.
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.
巨细胞病毒（CMV）感染是实体器官和骨髓移植后免疫抑制治疗常见的并发症。在大多数情况下，使用更昔洛韦进行预防和治疗是成功的，但近年来，对更昔洛韦耐药的CMV突变体感染频率有所增加。来氟米特是一种用于治疗风湿性疾病且具有抗病毒活性的免疫抑制药物，在这种情况下可能是一种有用的治疗选择。
一名60岁的CMV血清学阴性患者接受了来自CMV血清学阳性供体的肾移植。移植后出现2次经活检证实的移植排斥反应，采用类固醇冲击治疗，使病程复杂化。移植后4周诊断为CMV病毒血症。患者接受了静脉注射更昔洛韦和抗CMV免疫球蛋白治疗，并连续口服缬更昔洛韦。移植后6个月，患者因血液中病毒载量高确诊为CMV感染而入住我院。双倍剂量更昔洛韦和抗CMV免疫球蛋白治疗未能降低CMV病毒血症，因此我们诊断为更昔洛韦耐药的CMV感染。我们决定停用霉酚酸治疗，开始每日2次口服20mg来氟米特。该治疗使CMV病毒血症迅速下降并最终消失。来氟米特治疗期间肾移植功能保持稳定。观察到IgM和IgG抗CMV抗体均发生血清学转换。
对于肾移植受者中对更昔洛韦耐药的感染，来氟米特治疗是一种合理的选择，可有效清除病毒并重建适应性抗CMV免疫，且不会增加移植排斥的额外风险。
