Experiences With Leflunomide in Solid Organ Transplantation.

Williams, James W.; Huang, Wentao; Foster, Preston; Sankary, Howard; Mital, Deepak; Jensik, Stephen C.

doi:10.1097/00007890-200004271-00263

Cited by 37 publications

(68 citation statements)

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“…This has been cited as an explanation for significant variation in active metabolite pharmacokinetic features in a series of patients with chronic renal allograft dysfunction treated with leflunomide. 31 The patient's CMV DNAemia did reappear close to the time of her death, after a period of undetectability, but she had had leflunomide discontinued 4 weeks previously. It is unknown whether or not she might have achieved a durable remission from CMV if leflunomide could have been administered for a longer period of time.…”

Section: Discussionmentioning

confidence: 96%

“…34 In addition, the doses of leflunomide utilized in this patient were higher than those used in rheumatoid arthritis patients, and were based on the doses utilized in studies ;of leflunomide, and as an agent for rejection in solid-organ transplantation. 31 This patient did not have a liver biopsy performed due to severe thrombocytopenia. This complex clinical course does raise the question of whether leflunomide might have different toxicities when utilized in allogeneic bone marrow transplant recipients with GVHD of the liver, as compared with other groups of patients.…”

Section: Discussionmentioning

confidence: 98%

“…30 Leflunomide is increasingly recognized as a potent immunosuppressive agent for the prevention and treatment of rejection in solid organ transplant recipients. 31 It has also been reported to have novel anti-CMV activity in vitro, utilizing a mechanism different from that of other antiviral agents. 1,32 The mechanism of leflunomide antiviral activity is a topic of active research, but it does not appear to affect transcription of immediate-early or late viral genes or to inhibit viral DNA polymerase activity.…”

Section: Discussionmentioning

confidence: 99%

“…31 Liver toxicity has been reported in rheumatoid arthritis patients receiving leflunomide, generally in the form of transient liver function test abnormalities, although more serious liver disease has been reported in a patient receiving leflunomide and methotrexate. 34 In addition, the doses of leflunomide utilized in this patient were higher than those used in rheumatoid arthritis patients, and were based on the doses utilized in studies ;of leflunomide, and as an agent for rejection in solid-organ transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…More recent experience suggests that renal compromise may alter the efficacious blood level target 31 and patients with elevated serum creatinine may have substantially reduced protein binding; thus the effective (and toxic) level might be reduced. This has been cited as an explanation for significant variation in active metabolite pharmacokinetic features in a series of patients with chronic renal allograft dysfunction treated with leflunomide.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

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

Avery

Bolwell

Yen‐Lieberman

et al. 2004

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Avery

Bolwell

Yen‐Lieberman

et al. 2004

Bone Marrow Transplant

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Ganciclovir‐Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature

et al. 2017

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Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively. GR-CMV infection occurred ≤ 1 year posttransplantation in 11 patients (73%). All patients experienced dose reduction of valganciclovir (the oral prodrug of ganciclovir) before the development of GR-CMV. Initial treatment for GR-CMV included a variety of regimens, all including reduction in maintenance immunosuppression. Of the 6 patients with detectable GR-CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none received leflunomide. Of six patients with a LOS ≥ 14 days, 80% had CMV PCR below quantification on hospital discharge, and only one patient was readmitted in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50% rejection incidence, 27% graft loss, and 20% mortality. For patients with more than three admissions for GR-CMV treatment, 100% had a major complication: 60% rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and history of valganciclovir dose reduction. Overall, outcomes were poor. It appears that hospital readmission rate was reduced when CMV was treated to negativity with an initial treatment regimen of reduced immunosuppression, foscarnet, intravenous immunoglobulins, and leflunomide.

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Antivirals against human polyomaviruses: Leaving no stone unturned

Hirsch

2021

Reviews in Medical Virology

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Human polyomaviruses (HPyVs) encompass more than 10 species infecting 30%-90% of the human population without significant illness. Proven HPyV diseases with documented histopathology affect primarily immunocompromised hosts with manifestations in brain, skin and renourinary tract such as polyomavirus-associated nephropathy (PyVAN), polyomavirus-associated haemorrhagic cystitis (PyVHC), polyomavirus-associated urothelial cancer (PyVUC), progressive multifocal leukoencephalopathy (PML), Merkel cell carcinoma (MCC), Trichodysplasia spinulosa (TS) and pruritic hyperproliferative keratinopathy. Although virus-specific immune control is the eventual goal of therapy and lasting cure, antiviral treatments are urgently needed in order to reduce or prevent HPyV diseases and thereby bridging the time needed to establish virus-specific immunity. However, the small dsDNA genome of only 5 kb of the non-enveloped HPyVs only encodes 5-7 viral proteins. Thus, HPyV replication relies heavily on host cell factors, thereby limiting both, number and type of specific virus-encoded antiviral targets. Lack of cost-effective high-throughput screening systems and relevant small animal models complicates the preclinical development. Current clinical studies are limited by small case

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Experiences With Leflunomide in Solid Organ Transplantation.

Cited by 37 publications

References 0 publications

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

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

Ganciclovir‐Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature

Antivirals against human polyomaviruses: Leaving no stone unturned

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