Co-infection of Polyomavirus-BK and Cytomegalovirus in Renal Transplant Recipients

Toyoda, Mieko; Puliyanda, Dechu; Amet, Nurmamet; Baden, Lara; Cam, Vinh; Radha, Raju; Pao, Andy; Vo, Ashley; Bunnapradist, Suphamai; Moudgil, Asha; Jordan, Stanley C.

doi:10.1097/01.tp.0000165110.78397.93

Cited by 64 publications

(60 citation statements)

References 26 publications

(43 reference statements)

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“…All AEs were recorded and graded, in terms of relationship to study treatment and severity, as mild (does not interfere with patient's usual function), moderate (interferes to some extent with patient's usual function), or severe (interferes significantly with patient's usual function). Laboratory safety evaluations, including assessment of blood Epstein-Barr virus (EBV) DNA levels (average value from 2 separate assays expressed as copies/500 mg of DNA) by quantitative polymerase chain reaction of total DNA, as previously described (19), and vital-sign assessments were carried out at screening (14-28 days prior to baseline), baseline, weeks 1, 2, 4, and 6, and at the 2 followup visits (weeks 8 and 12). Electrocardiograms were obtained at screening and at weeks 1, 2, 4, and 6.…”

Section: Methodsmentioning

confidence: 99%

The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double‐blind, placebo‐controlled phase IIa trial of three dosage levels of CP‐690,550 versus placebo

Kremer

Bloom

Breedveld

et al. 2009

Arthritis & Rheumatism

500

230

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Objective. To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response.Methods. Patients (n ‫؍‬ 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks.Results. By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and highdensity lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms.Conclusion. Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.ClinicalTrials.gov identifier: NCT00147498.

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Section: Methodsmentioning

confidence: 99%

The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double‐blind, placebo‐controlled phase IIa trial of three dosage levels of CP‐690,550 versus placebo

Kremer

Bloom

Breedveld

et al. 2009

Arthritis & Rheumatism

500

230

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“…donor CMV seropositive and recipient CMV seronegative. While co-infection of polyomavirus and cytomegalovirus have been reported in renal transplant recipients [28,29] and after stem cell transplantation [30], the impact of recipient CMV seropositivity without evidence of CMV viremia on polyomavirus infection is unknown. However, in a study of 132 hematopoietic stem cell transplant recipients a positive recipient CMV serostatus and the underlying disease emerged as the only risk factors associated with BK viremia [31].…”

Section: Discussionmentioning

confidence: 99%

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

et al. 2013

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BackgroundPolyomavirus BK nephropathy (PyVAN) remains an important cause of early graft dysfunction and graft loss in kidney transplantation.MethodsIn this retrospective, single centre cohort study we studied the incidence and outcome of BK viral infection in 352 patients transplanted in 2008–2011.ResultsDuring follow-up viral replication was detected in 48 patients (13.6%); 22 patients (6.2%) had biopsy proven PyVAN.In multivariate logistic regression analyses risk factors for BK-viremia were lack of enrolment into randomized controlled trials (RCTs), biopsy proven acute rejections, cytomegaly virus (CMV) serostatus of both donor and recipient and previous transplantation.In patients without PyVAN reduction or switch of immunosuppression was associated with rapid viral clearance and stable graft function. In contrast, in most patients with PyVAN graft function deteriorated and 5 patients prematurely lost their allograft. Switch of immunosuppression to a low dose cyclosporine plus mTOR inhibitor based regimen in patients with PyVAN was safe, well tolerated and tended to be associated with a better short-term outcome in terms of graft function compared to reduction of existing immunosuppression alone.ConclusionsWith the lack of licensed anti-polyoma viral drugs reduction or conversion of immunosuppression remains the mainstay of therapy in patients with PyVAN. The combination of low dose cyclosporine plus mTOR inhibition appears to be safe and warrants further investigation.

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“…3 Diastolic function may be preserved on echocardiography despite restrictive physiology and it does not appear to be a reliable surrogate for echocardiographic diagnosis of IOC. Two patients with the dilated phenotype and HFrEF had only partial reversal of their LV dysfunction with institution of iron chelation therapy.…”

Section: Supporting Informationmentioning

confidence: 99%

“…To this aim, we have devised a robust transcriptomic analysis to identify genes upregulated in relapsed patients and drug-resistant AML cell lines and linearly associated with patient survival in multivariable analysis. We have found that (1) the expression of Vanin 1 (VNN1), an anti-apoptotic enzyme inhibiting caspases and scavenging reactive oxygen species, 3 is significantly associated with relapse-, event-, or disease-free survival Figure S1). The resulting 6 differentially-regulated genes (DRGs, SPINK2, TM4SF1, VNN1, SYTL4, BEX1, TEAD4) were then inputted into a Cox proportional hazards (Cox-PH) model of patients' disease-free survival (DFS) that also included age, gender, karyotypical abnormalities, French-AmericanBritish (FAB) subgroups and major driver mutations (Supporting Information Table S1).…”

mentioning

confidence: 99%

Vanin 1 (VNN1) levels predict poor outcome in acute myeloid leukemia

et al. 2017

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without urogenital symptoms are more frequent. We found no case of adenoviruria after stem cell transplantation, so we must conclude that this virus is not that important in the adult population like it is in paediatric stem cell transplantation.5 Interestingly, BK viruria was significantly associated with acute renal failure. Acute renal failure was described in retrospective analysis before, so we must conclude that BK virus can also lead to nephropathy in allogeneic stem cell transplantation like it is well known in kidney transplantation. 4 We found no association with polyomavirus BK and JC with GvHD contrary to what was described in other studies. 6 Regarding GvHD prophylaxis, our study was quite homogenous, since all patients received alemtuzumab.Other studies had more heterogenous populations or all participants received antithymogloboline for GvHD prophylaxis. 6 We conclude that urological complications, especially polyomavirus associated urogenital infections, are important and considerable during adult allogeneic stem cell transplantation. ACKNOWLEDGMENTSThe authors would like to thank all participating patients and all nurses or study nurses of the University Medicine Greifswald Department of Hematology/Oncology who made this study a success. Thank you for your great help and advice! ORCID Laila Schneidewind

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Co-infection of Polyomavirus-BK and Cytomegalovirus in Renal Transplant Recipients

Cited by 64 publications

References 26 publications

The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double‐blind, placebo‐controlled phase IIa trial of three dosage levels of CP‐690,550 versus placebo

The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double‐blind, placebo‐controlled phase IIa trial of three dosage levels of CP‐690,550 versus placebo

BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

Vanin 1 (VNN1) levels predict poor outcome in acute myeloid leukemia

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