TY - JOUR
T1 - Utility of leflunomide in the treatment of complex cytomegalovirus syndromes
AU - Avery, Robin K.
AU - Mossad, Sherif B.
AU - Poggio, Emilio
AU - Lard, Michelle
AU - Budev, Marie
AU - Bolwell, Brian
AU - James Waldman, W.
AU - Braun, William
AU - Mawhorter, Steven D.
AU - Fatica, Richard
AU - Krishnamurthi, Venkatesh
AU - Young, James B.
AU - Shrestha, Rabin
AU - Stephany, Brian
AU - Lurain, Nell
AU - Yen-Lieberman, Belinda
PY - 2010/8/27
Y1 - 2010/8/27
N2 - Background. Cytomegalovirus (CMV) viremia that is resistant or refractory to the standard antiviral therapy still constitutes a major threat to high-risk transplant recipients. In addition, multiple CMV recurrences may lead to neutropenia because of repeated courses of therapy with ganciclovir derivatives. Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV activity. This study reports on its use in 17 transplant recipients with complex CMV syndromes who had failed or were intolerant to other therapies. Methods. Single-center, retrospective study. Clinical data were extracted from the electronic medical record. CMV DNA viral loads were performed by quantitative hybrid capture assay. Results. Leflunomide was initiated after a median of three episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL. Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9 of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher peak viral load and higher viral load at the start of leflunomide therapy were associated with failure to suppress viremia. The duration of leflunomide therapy ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months), and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects included diarrhea (35%), anemia (18%), and increased liver function tests (12%). Conclusions. Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.
AB - Background. Cytomegalovirus (CMV) viremia that is resistant or refractory to the standard antiviral therapy still constitutes a major threat to high-risk transplant recipients. In addition, multiple CMV recurrences may lead to neutropenia because of repeated courses of therapy with ganciclovir derivatives. Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV activity. This study reports on its use in 17 transplant recipients with complex CMV syndromes who had failed or were intolerant to other therapies. Methods. Single-center, retrospective study. Clinical data were extracted from the electronic medical record. CMV DNA viral loads were performed by quantitative hybrid capture assay. Results. Leflunomide was initiated after a median of three episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL. Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9 of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher peak viral load and higher viral load at the start of leflunomide therapy were associated with failure to suppress viremia. The duration of leflunomide therapy ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months), and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects included diarrhea (35%), anemia (18%), and increased liver function tests (12%). Conclusions. Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.
KW - CMV
KW - antiviral therapy
KW - ganciclovir resistance
KW - leflunomide
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U2 - 10.1097/TP.0b013e3181e94106
DO - 10.1097/TP.0b013e3181e94106
M3 - Article
C2 - 20683281
AN - SCOPUS:77955980893
VL - 90
SP - 419
EP - 426
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 4
ER -