Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection

• Published in: Bone marrow transplantation (Basingstoke) Vol. 34; no. 12; pp. 1071 - 1075
• Main Authors: AVERY, R. K, BOLWELL, B. J, CURTIS, J, KALAYCIO, M, POHLMAN, B, WILLIAMS, J. W, YEN-LIEBERMAN, B, LURAIN, N, WALDMAN, W. J, LONGWORTH, D. L, TAEGE, A. J, MOSSAD, S. B, KOHN, D, LONG, J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.12.2004
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Arthritis; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone Marrow Transplantation - adverse effects; Bone marrow, stem cells transplantation. Graft versus host reaction; Case studies; Cidofovir; Complications; Complications and side effects; Cytomegalovirus; Cytomegalovirus infections; Cytomegalovirus Infections - drug therapy; Deoxyribonucleic acid; Diagnosis; DNA; Dosage and administration; Drug Resistance, Viral; Drug therapy; Drug Therapy, Combination; Fatal Outcome; Female; Foscarnet; Foscarnet - therapeutic use; Ganciclovir; Graft rejection; Graft versus host disease; Graft vs Host Disease; Graft-versus-host reaction; Health services; Humans; Immunosuppressive agents; Immunosuppressive Agents - therapeutic use; Infections; Isoxazoles - therapeutic use; Leflunomide; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - complications; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Liver; Liver diseases; Liver Failure; Liver transplantation; Medical sciences; Middle Aged; Patient outcomes; Patients; Pharmacology. Drug treatments; Rheumatoid arthritis; Risk factors; Salvage Therapy - methods; Stem cell transplantation; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Viral Load - methods; United States; Prostaglandin-endoperoxide synthase; Isoxazole derivatives; Stem cell; Hematopoietic cell; Homograft; Leflunomide; Betaherpesvirinae; Bone marrow; Graft; Antiviral; Antirheumatic agent; Human; Cytomegalovirus; Treatment resistance; antiviral resistance; Enzyme; Herpesviridae; Enzyme inhibitor; Recipient; Infection; Virus; Non steroidal antiinflammatory agent; Case study; Chemotherapy; Treatment; Viral disease; Oxidoreductases; Immunosuppressive agent
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1704694

Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.