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JOURNAL ARTICLE
Francis Ayuk, Eva-Maria Wagner-Drouet, Daniel Wolff, Natascha von Huenerbein, Ute-Marie von Pein, Evgeny Klyuchnikov, Stephanie von Harsdorf, Christian Koenecke, Herbert Sayer, Nicolaus Kröger
Although most patients with chronic graft-versus-host disease (cGVHD) show initial response to first-line therapy, long-term clinically meaningful success of first-line treatment remains rare. In a prospective multicentre phase II trial in 6 German centers, patients with newly diagnosed moderate or severe cGVHD received prednisone and everolimus for 12 months followed by a 1-year follow-up period. Primary endpoint was treatment success (TS) at 6 months defined as patient being alive, achieving PR or CR of cGVHD, having no relapse of underlying disease and requiring no secondary treatment for cGVHD...
May 2, 2024: Bone Marrow Transplantation
#2
JOURNAL ARTICLE
Victor Joo, Karim Abdelhamid, Alessandra Noto, Sofiya Latifyan, Federica Martina, Douglas Daoudlarian, Rita De Micheli, Menno Pruijm, Solange Peters, Roger Hullin, Olivier Gaide, Giuseppe Pantaleo, Michel Obeid
The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69)...
April 30, 2024: Nature Communications
#3
JOURNAL ARTICLE
Daysi Sanmartin, Camilo Tamayo, Luis Esteban Orozco, Angélica Ordóñez, Juliana Huertas, Diego Ávila, Johanna Echeverry, Mónica Caicedo, Paola García
OBJECTIVES: To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system. METHODS: A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons...
April 24, 2024: Value in Health Regional Issues
#4
JOURNAL ARTICLE
Markus Benedikt Krueger, Agnes Bonifacius, Anna Christina Dragon, Maria Michela Santamorena, Björn Nashan, Richard Taubert, Ulrich Kalinke, Britta Maecker-Kolhoff, Rainer Blasczyk, Britta Eiz-Vesper
Infectious complications, including widespread human cytomegalovirus (CMV) disease, frequently occur after hematopoietic stem cell and solid organ transplantation due to immunosuppressive treatment causing impairment of T-cell immunity. Therefore, in-depth analysis of the impact of immunosuppressants on antiviral T cells is needed. We analyzed the impact of mTOR inhibitors sirolimus (SIR/S) and everolimus (EVR/E), calcineurin inhibitor tacrolimus (TAC/T), purine synthesis inhibitor mycophenolic acid (MPA/M), glucocorticoid prednisolone (PRE/P) and common double (T+S/E/M/P) and triple (T+S/E/M+P) combinations on antiviral T-cell functionality...
2024: Transplant International
#5
JOURNAL ARTICLE
Kyu-Sun Lee, Hyungseop Kim, Sun Hwa Lee, Dong-Ju Choi, Minjae Yoon, Eun-Seok Jeon, Jin-Oh Choi, Jeehoon Kang, Hae-Young Lee, Sung-Ho Jung, Jaewon Oh, Seok-Min Kang, Soo Yong Lee, Min Ho Ju, Jae-Joong Kim, Myoung Soo Kim, Hyun-Jai Cho
The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3...
2024: Transplant International
#6
JOURNAL ARTICLE
Tim Richardson, Christof Scheid, Marco Herling, Lukas P Frenzel, Carmen Herling, Marta Rebecca Cruz Aguilar, Sebastian Theurich, Michael Hallek, Udo Holtick
BACKGROUND: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft-versus-tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti-cancer immune response...
April 14, 2024: European Journal of Haematology
#7
JOURNAL ARTICLE
Paolo De Simone, Arianna Precisi, Quirino Lai, Juri Ducci, Daniela Campani, Piero Marchetti, Stefano Gitto
To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus...
March 22, 2024: Cancers
#8
JOURNAL ARTICLE
Takashi Sakaguchi, Akihiko Mitsuke, Yoichi Osako, Yasutoshi Yamada, Himawari Takeyama, Risako Ogawa, Katsuya Takahashi, Yukiko Hirohata, Sayuri Yamamoto, Junya Arima, Wataru Fukumoto, Satoshi Sugita, Satoru Inoguchi, Ryosuke Matsushita, Hirofumi Yoshino, Shuichi Tatarano, Hideki Enokida
BACKGROUND: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods. METHODS: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed...
April 8, 2024: BMC Nephrology
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JOURNAL ARTICLE
Josquin Moraly, Julien Rossignol, Claire Rouzaud, Thomas Gabas, Hassiba Bouktit, Ludovic Lhermitte, Danielle Canioni, Sylvie Fraitag, Julie Bruneau, Stéphane Barete, Felipe Suarez, Thomas Ballul, Cécile Meni, Laura Polivka, Louis Terriou, David Launay, Laurence Bouillet, Caroline Gaudy-Marqueste, Marie Gousseff, Edwige Le Mouel, Antoine Neel, Dana Ranta, Roland Jaussaud, Philippe Guilpain, Laurent Frenzel, Julie Agopian, Patrice Dubreuil, Céline Greco, Sophie Dimicoli-Salazar, Mael Heiblig, Clément Gourguechon, Olivier Tournilhac, Rose-Marie Javier, Florence Castelain, Quentin Cabrera, Marie Pierre Gourin, Ewa Wierzbicka-Hainaut, Jose Miguel Torregrosa-Diaz, Cristina Bulai, Christian Lavigne, Cyrille Hoarau, Michel Arock, Gandhi Damaj, Olivier Lortholary, Olivier Hermine
Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM...
April 6, 2024: American Journal of Hematology
#10
JOURNAL ARTICLE
Hirak Pahari, Amruth Raj, Ambreen Sawant, Dipak S Ahire, Raosaheb Rathod, Chetan Rathi, Tushar Sankalecha, Sachin Palnitkar, Vikram Raut
BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM: To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future...
March 18, 2024: World Journal of Transplantation
#11
JOURNAL ARTICLE
Bahar Naseri, Amirhossein Mardi, Arezou Khosrojerdi, Elham Baghbani, Leili Aghebati-Maleki, Amirhossein Hatami-Sadr, Javad Ahmadian Heris, Shabnam Eskandarzadeh, Mahshid Kafshdouz, Nazila Alizadeh, Behzad Baradaran
BACKGROUND: Antigen-specific T-cell immunity is provided by dendritic cells (DCs), which are specialized antigen-presenting cells. Furthermore, they establish a link between innate and adaptive immune responses. Currently, DC modification is a new approach for the therapy of several disorders. During solid organ transplantation, Everolimus, which is a mammalian target of rapamycin (mTOR) inhibitor, was initially utilized to suppress the immune system's functionality. Due to the intervention of Everolimus in various signaling pathways in cells and its modulatory properties on the immune system, this study aims to investigate the effect of treatment with Everolimus on the maturation and expression of immune checkpoint genes in monocyte-derived DCs...
April 1, 2024: Human Immunology
#12
JOURNAL ARTICLE
Tomoyuki Sakaue, Kazuhiro Yamamoto, Kotaro Itohara, Yumi Kitahiro, Takahito Endo, Naoki Yokoyama, Takeshi Ishimura, Tomohiro Omura, Ikuko Yano
Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption...
March 12, 2024: Drug Metabolism and Pharmacokinetics
#13
JOURNAL ARTICLE
Vienne Pinlac, Lynn Bonifacio
BACKGROUND: Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is achieved when a patient who has discontinued tyrosine-kinase inhibitor treatment sustains major molecular response (MMR) and does not require restarting therapy. The feasibility of kidney transplantation (KT), and achieving TFR post-transplantation in patients with a pre-existing CML, are currently not well-studied. METHODS: We describe the clinical course of a 39-year-old Filipino woman with IgA nephropathy who developed CML during treatment...
March 26, 2024: Transplantation Proceedings
#14
JOURNAL ARTICLE
Jan Johnson, Wendy Somerfield, Simon R Johnson
BACKGROUND: Lymphangioleiomyomatosis (LAM) is common in tuberous sclerosis complex (TSC) yet under recognised with management mostly based upon evidence obtained from patients with sporadic LAM. We performed a prospective audit of patients with TSC-LAM attending a national referral centre to inform management guidelines. METHODS: The UK LAM Centre was established in 2011 and conducts a prospective audit of pre-defined quality outcomes for all subjects. Audit data are reported on all patients with TSC-LAM and a comparator population of patients with sporadic LAM...
March 26, 2024: Orphanet Journal of Rare Diseases
#15
JOURNAL ARTICLE
Kannan Sridharan, Shamik Shah, Mona Al Hammad, Fatima Ali Mohammed, Sindhan Veeramuthu, Mona Abdulla Taher, Mustafa Mohamed Hammad, Lamees Jawad, Eman Farid
Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function...
March 26, 2024: Journal of Biomedical Research
#16
JOURNAL ARTICLE
Mark S Obri, Alan M Fahoury, Suhaib Alhaj Ali, Momin Samad, Spandana Alluri, Alex S Obri, Mohamed Ramzi Almajed, Kevin B Harris, Syed-Mohammed Jafri
This retrospective study aims to evaluate the safety of everolimus when used as part of the immunosuppression regimen in patients who underwent liver transplant from 2009 to 2019 at a tertiary liver transplant center. Patients were divided into two groups: those who received everolimus as part of the post-transplant regimen and those who did not. The primary safety outcome measured was the development of new pulmonary complications that had been associated with everolimus use in prior studies. Lung function was determined by pulmonary function tests if available or CT scans of the chest...
January 2024: Curēus
#17
JOURNAL ARTICLE
Hannah Kreienbaum, Brigitte Stiller, Rouven Kubicki, Alexej Bobrowski, Johannes Kroll, Thilo Fleck
BACKGROUND: Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX. METHODS: Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1-17.9) years transplanted between 2008 and 2020...
March 2024: Pediatric Transplantation
#18
JOURNAL ARTICLE
Marta Carretero-Ledesma, Manuela Aguilar Guisado, Judith Berastegui-Cabrera, María Balsera-Manzanero, Jerónimo Pachón, Elisa Cordero, Javier Sánchez-Céspedes
Human adenovirus (HAdV) and cytomegalovirus (HCMV) are cause of high morbidity and mortality in patients receiving solid organ (SOT) and hematopoietic stem cell transplantations (HSCT). Immunosuppressors are universally used to prevent graft-versus-host disease (GVHD) in HSCT and graft rejection in SOT. The long-term use of these drugs is associated with a high risk of infections, but there are also evidences of their specific interference with virus infection. The antiviral activity of immunosuppressors commonly used in the clinical practice in SOT and HSCT recipients has been evaluated in vitro to determine whether their use could be associated with less risk of HAdV and HCMV infection...
February 22, 2024: International Journal of Antimicrobial Agents
#19
Giuliano Ponis, Giuliana Decorti, Egidio Barbi, Gabriele Stocco, Massimo Maschio
Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation...
February 17, 2024: International Journal of Molecular Sciences
#20
JOURNAL ARTICLE
Jérôme Dumortier, Olivier Boillot
BACKGROUND: After organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The present study aimed to evaluate the safety and efficacy of conversion from everolimus (EVR) twice daily to sirolimus (SIR) once daily in a large cohort of liver transplantation (LT) patients. METHODS: Were included 108 LT patients with at least 12 months of post-transplant follow-up and no rejection episodes in the last year...
February 21, 2024: Transplant Immunology
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