Everolimus transplantation

It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. Among the most common issues is the development of ulcers of the oral mucosa (mTOR-inhibitor associated stomatitis; mIAS). These lesions are distinct from those of other anti-cancer agents, occur with regularity, and impact patient outcomes...

Solid organ transplant recipients face an increased risk of dyslipidemia, which contributes to cardiovascular complications. Commonly used drugs such as ciclosporin and tacrolimus can aggravate and cause dyslipidemia. Immunosuppressive drugs particularly ciclosporin and tacrolimus are also known to worsendyslipidemia in transplant recipients. Mammalian target of rapamycin (mTOR) inhibitors like sirolimus and everolimus also alter lipid metabolism. Lifestyle and dietary modifications should be encouraged. Careful consideration of immunosuppressant choices is also vital to control dyslipidemia...

BACKGROUND: Cardiac allograft vasculopathy (CAV) is still the main drawback of heart transplantation (HTx) and percutaneous coronary intervention (PCI) is a palliative measure because of the high incidence of failure. OBJECTIVE: This study aimed to investigate the safety and efficacy of bioresorbable scaffolds (BRSs) as potential novel therapeutic tool for the treatment of coronary stenoses in CAV. METHODS: This is a multicenter, single-arm, prospective, open-label study (CART, NCT02377648), that included patients affected by advanced CAV treated with PCI and second-generation ABSORB BRS (Abbott Vascular)...

INTRODUCTION: Patients with relapsing or primary refractory Hodgkin lymphoma, still have unsatisfactory outcomes after high dose chemotherapy followed by autologous stem cell transplantation (ASCT). Brentuximab Vedotin (BV) is the only approved agent for maintenance therapy for up to one year in these patients, however, this agent is often not available or affordable for many patients, especially in the developing countries. In this study, we used Everolimus as maintenance therapy after ASCT among patients with relapsing/refractory Hodgkin lymphoma...

Background and Objectives : Underpowered immune response to vaccines against SARS-CoV-2 was observed in solid organ transplant (SOT) recipients. A novel combination of monoclonal antibodies tixagevimab-cilgavimab (TGM/CGM) received authorization as pre-exposure prophylaxis (PrEP) in those with reduced response to vaccine. We aimed to evaluate the response rate to COVID-19 vaccination in kidney transplant (KT), compared to liver transplant (LT) recipients, and the efficacy and safety of PrEP with TGM/CGM. Material and Methods : Between March and November 2022, adult KT and LT recipients who had completed the vaccination schedule (3 doses) were tested for anti-SARS-CoV-2 antibodies titer...

BACKGROUND: Natural killer (NK) cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance, viral infection, or tumor recurrence. Immunosuppression consists of a triple drug standard regimen comprising tacrolimus (TAC) and corticosteroids (CS) with either mycophenolate mofetil (MMF) or sirolimus (SIR)/everolimus (EVE). The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor (mTORI)...

Plasma creatinine phosphokinase (CPK) elevation is frequent after heart transplantation. In the present study, we tested the hypothesis that this CPK elevation is related to idiopathic cardiomyopathy as primary cardiac disease. We included 203 patients who survived >1 year after heart transplantation. Plasma CPK was measured every 4 months during a 15.1 ± 7.7-year follow-up. In univariate analysis, CPK elevation was significantly associated with age at transplantation, length of follow-up, treatment with everolimus, and idiopathic cardiomyopathy as primary cardiac disease...

Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs available to treat HCMV infection, targeting viral polymerase, whose use is complicated by toxicity and the emergence of resistance. Maribavir and letermovir are the latest antivirals to have been developed with other targets. The approval of letermovir represents an important innovation for CMV prevention in hematopoietic stem cell transplant recipients, whereas maribavir allowed improving the management of refractory or resistant infections in transplant recipients...

Cyclosporine A, everolimus, sirolimus, and tacrolimus are the most commonly used immunosuppressant drugs in organ transplant and auto-immune patients. The narrow therapeutic window of these immunosuppressant drugs requires close monitoring of drug blood levels to ensure proper therapeutic response. A quick, robust high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was introduced for monitoring whole blood levels of these immunosuppressant drugs with the use of the MassTrak™ Immunosuppressant kit...

INTRODUCTION: Cytomegalovirus (CMV) infection is a widespread condition that can affect individuals of all ages. Most cases of CMV infection are mild and resolve on their own. However, in immunocompromised individuals, such as post-transplant patients or those with cancer, severe infections can occur. While there have been several studies on CMV infection in post-transplant patients, there is limited literature on CMV infection in cancer, particularly in kidney cancer. Case Report . In this case report, we present the case of a 61-year-old man with clear cell renal cell carcinoma who underwent targeted therapy with the receptor tyrosine kinase (RTK) inhibitor lenvatinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus...

BACKGROUND: Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration. METHODS: This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS)...

Background : The role of tailored immunosuppression (IS) in the development of the humoral response (HR) to SARS-CoV-2 mRNA-based vaccination in liver transplant (LT) recipients is unknown. Methods : This is a single-centre prospective study of patients who underwent LT between January 2015 and December 2021 and who have received three doses of mRNA-based SARS-CoV-2 vaccination. Patients undergoing Tacrolimus-based immunosuppression (TAC-IS) were compared with those undergoing Everolimus-based immunosuppression (EVR-IS)...

The mechanistic target of rapamycin complex 1 (mTORC1) inhibitor everolimus is one of the few approved therapies for locally advanced and metastatic neuroendocrine tumours (NETs). However, after initial disease stabilisation, most patients develop resistance within 1 year. Our aim was to overcome resistance to everolimus by additional treatment with the PI3K-alpha inhibitor alpelisib in an everolimus-resistant orthotopic pancreatic neuroendocrine carcinoma xenograft mouse model. Female SCID mice underwent laparoscopic pancreatic transplantation of everolimus-sensitive (BON1KDMSO) or everolimus-resistant (BON1RR2) NET cells...

IMPORTANCE: Solid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19-related severity in this population are still insufficiently explored in the literature. OBJECTIVE: To examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19-related hospitalization in solid organ transplant recipients...

INTRODUCTION: Hemoadsorption shows promising signals in organ preservation and post lung transplantation. However, its potential impact on the pharmacokinetics of immunosuppressant drugs (ID) is still unknown. METHODS: In this interventional study, CytoSorb® hemoperfusion was tested in healthy sheep ( n  = 5) against a sham extracorporeal circuit ( n  = 3). Seven different ID (tacrolimus (TAC), cyclosporin A (CYA), mycophenolate mofetil (MMF), everolimus (EVER), basiliximab (BAS), methylprednisolone (MP) and prednisolone (PRED)) were administered in clinically relevant doses and combinations...

OBJECTIVE: Sirolimus (SRL) and everolimus (EVL) are increasingly included in immunosuppressive protocols after heart transplantation. They present some side effects, including the appearance of painful lesions in the oral cavity. Therefore, this systematic review aimed to verify the global prevalence and clinical characteristics of oral lesions induced by SRL and EVL in heart transplant patients. STUDY DESIGN: A systematic review was performed using 5 main electronic databases (Medline/PubMed, SCOPUS, EMBASE, Web of Science, and LILACS), in addition to the gray literature...

Epstein-Barr virus (EBV) can rarely induce smooth muscle tumors (SMTs). A 20-year-old female patient underwent kidney transplantation for renal failure. Since then, she has been treated with immunosuppressants, including a calcineurin inhibitor, tacrolimus, and prednisolone, owing to the immunological rejection. Three years later, she developed large liver tumors (diameter >5 cm) and multiple small lung tumors that were identified as EBV-SMTs based on the results of liver biopsy/histopathology. No intervention was performed except for the addition of a mammalian target of the rapamycin inhibitor, everolimus, which inhibits both immune reaction and SMT growth...

All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017...

No studies have examined the impact of multimorbidity and socioeconomic position (SEP) on adherence to the pharmacological therapies following heart transplantation (HTx). Using nationwide Danish registers, we tested the hypothesis that multimorbidity and SEP affect treatment patterns and adherence to pharmacological therapies in first-time HTx recipients. Pharmacological management included cost-free immunosuppressants and adjuvant medical treatment (preventive and hypertensive pharmacotherapies; loop diuretics)...

OBJECTIVES: This study aimed to determine the predictive factors of BK virus viremia/nephropathy in kidney transplant recipients and to evaluate the effects of low-dose tacrolimus plus everolimus. MATERIALS AND METHODS: This study included 3654 kidney transplant recipients. The patients were divided into 2 groups: group 1 were BK virus negative (n = 3525, 96.5%) and group 2 were BK virus positive (n = 129, viremia 3.5%, nephropathy 1%). Predictive factors were determined by receiver operating characteristic curve analysis and logistic regression models...