Leflunomide therapy for refractory cytomegalovirus infections in hematopoietic stem cell transplant recipients.

Background Currently, there are no prospective, randomized trials analyzing leflunomide for the treatment of cytomegalovirus infection or disease in allogeneic stem cell transplant patients. Objective The primary objective of this case series was to determine the clinical and virological responses of utilizing leflunomide as therapy for refractory cytomegalovirus infections, unresponsive to first-line therapy in allogeneic stem cell transplant patients. Additionally, patient and leflunomide specific characteristics were identified and determined in this descriptive case series. Methods This is a single-center, case series of adult allogeneic stem cell transplant patients with refractory cytomegalovirus infections receiving leflunomide between 1 January 2005 and 31 March 2015. Results A total of 14 patients with refractory cytomegalovirus infections received leflunomide. All patients received concurrent anti-cytomegalovirus therapy. Nine of 13 patients tested positive for phosphotransferase UL97 and/or viral DNA polymerase UL54 genotype mutations. Nine patients achieved a virological response with undetectable cytomegalovirus titers. Of the 13 patients with teriflunomide serum levels, eight patients maintained levels >40 micrograms/milliliter (mcg/mL). Common adverse effects were pancytopenia (n = 8) and elevated liver function tests (n = 4). Conclusions Despite current strategies, refractory or recurrent cytomegalovirus infection and disease remain a clinical challenge to treat in the stem cell transplant patient population. Leflunomide used in combination with other concomitant therapies use for refractory cytomegalovirus infection in clinical practice may be a safe and effective option in the allogeneic stem cell transplant patient population.