Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.
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.
Department of Infectious Disease, Cleveland Clinic Foundation, Desk S-32, 9500 Euclid Avenue, Cleveland, OH 44195, USA. averyr@ccf.org
R K
RK
Avery
B J
BJ
Bolwell
B
B
Yen-Lieberman
N
N
Lurain
W J
WJ
Waldman
D L
DL
Longworth
A J
AJ
Taege
S B
SB
Mossad
D
D
Kohn
J R
JR
Long
J
J
Curtis
M
M
Kalaycio
B
B
Pohlman
J W
JW
Williams
D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D006086:Graft vs Host Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000628:therapy; D017093:Liver Failure; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods*; D014184:Transplantation, Homologous; D019562:Viral Load / Q000379:methods
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D017245:Foscarnet; D000077339:Leflunomide