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

J Oncol Pharm Pract. 2019 Oct;25(7):1731-1737. doi: 10.1177/1078155218796188. Epub 2018 Aug 31.


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.

Keywords: Cytomegalovirus; hematopoietic stem cell transplant; leflunomide.

MeSH terms

  • Adult
  • Aged
  • Cytomegalovirus Infections / drug therapy*
  • DNA, Viral
  • DNA-Directed DNA Polymerase / genetics
  • Female
  • Genotype
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Leflunomide / administration & dosage*
  • Male
  • Middle Aged
  • Mutation
  • Retrospective Studies
  • Viral Proteins / genetics
  • Young Adult


  • DNA, Viral
  • UL54 protein, Human herpesvirus 5
  • Viral Proteins
  • DNA-Directed DNA Polymerase
  • Leflunomide