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Bernard P Mahon - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells in Solid Organ Transplantation misot fourth meeting lessons learned from first clinical trials
Transplantation, 2013Co-Authors: Marcella Franquesa, Martin J. Hoogduijn, Elke Eggenhofer, Marlies E.j. Reinders, A U Engela, F Mensah, J Torras, Antonello Pileggi, Cees Van Kooten, Bernard P MahonAbstract:textabstractThe Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem cells as a therapeutic agent in Solid Organ Transplantation and emphasizes the issues (proper timing, concomitant immunossupression, source and immunogenicity of mesenchymal stem cells, and oncogenicity) that have been addressed and will be followed up by the MiSOT Consortium in future studies.
Eric A Engels - One of the best experts on this subject based on the ideXlab platform.
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cancer risk after pediatric Solid Organ Transplantation
Pediatrics, 2017Co-Authors: Elizabeth L Yanik, Jodi M Smith, Meredith S Shiels, Christina A Clarke, Charles F Lynch, Amy R Kahn, Lori Koch, Karen Pawlish, Eric A EngelsAbstract:BACKGROUND: The effects of pediatric Solid Organ Transplantation on cancer risk may differ from those observed in adult recipients. We described cancers in pediatric recipients and compared incidence to the general population. METHODS: The US transplant registry was linked to 16 cancer registries to identify cancer diagnoses among recipients RESULTS: Among 17 958 pediatric recipients, 392 cancers were diagnosed, of which 279 (71%) were NHL. Compared with the general population, incidence was significantly increased for NHL (SIR = 212, 95% confidence interval [CI] = 188–238), Hodgkin’s lymphoma (SIR = 19, 95% CI = 13–26), leukemia (SIR = 4, 95% CI = 2–7), myeloma (SIR = 229, 95% CI = 47–671), and cancers of the liver, soft tissue, ovary, vulva, testis, bladder, kidney, and thyroid. NHL risk was highest during the first year after Transplantation among recipients CONCLUSIONS: Pediatric recipients have a markedly increased risk for many cancers. NHL constitutes the majority of diagnosed cancers, with the highest risk occurring in the first year after Transplantation. NHL risk was high in recipients susceptible to primary EBV infection after transplant and in intestine transplant recipients, perhaps due to EBV transmission in the donor Organ.
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risk of merkel cell carcinoma after Solid Organ Transplantation
Journal of the National Cancer Institute, 2015Co-Authors: Christina A Clarke, Margaret M. Madeleine, Charles F Lynch, Karen Pawlish, Hilary A Robbins, Zaria Tatalovich, Jack L Finch, Brenda Y Hernandez, Joseph F Fraumeni, Eric A EngelsAbstract:Merkel cell carcinoma (MCC) is an uncommon skin cancer of neuroendocrine differentiation. MCC behaves aggressively, and five-year relative survival is only 62% (1). Like other skin cancers, MCC largely affects light-skinned populations (2,3), especially those highly exposed to ultraviolet radiation (UVR) (4). Recently, a previously unknown virus, Merkel cell polyomavirus (MCV), was detected in most but not all MCC tumors tested (5). This discovery has revived interest in MCC epidemiology, especially regarding the role of impaired immunity in promoting viral carcinogenesis. However, details regarding the relevant type of immunosuppression are poorly understood. Immunosuppression is suspected as important to MCC causation, as risk is increased among persons with human immunodeficiency virus (HIV) (6,7), chronic lymphocytic leukemia, (3,8) and other hematologic malignancies (8). MCC risk is also elevated following Solid Organ Transplantation (9–12), after which patients must be pharmacologically immunosuppressed to prevent graft rejection. Also, some immunosuppressant medications used in Transplantation may have direct skin carcinogenic effects, including interacting with UVR to enhance DNA damage (13–18). These direct effects may relate to the very high risks of squamous cell skin cancers in transplant recipients (19). Prior studies of transplant-related MCC have included fewer than 50 case patients and have not provided information on how risk differs by age, timing of transplant, or specific immunosuppressive medications (9–12). In the present study, we evaluated the occurrence of MCC among Solid Organ transplant recipients in the Transplant Cancer Match (TCM) Study, a large, population-based cohort of US transplant recipients for which cancer ascertainment was conducted uniformly via linkage with cancer registries. We quantified MCC risk overall and according to recipient demographic characteristics, transplanted Organ, UVR exposure based on place of residence, length of time since transplant, and type of immunosuppressive drugs received.
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cumulative incidence of cancer after Solid Organ Transplantation
Cancer, 2013Co-Authors: Erin C Hall, Ruth M Pfeiffer, Dorry L Segev, Eric A EngelsAbstract:BACKGROUND Solid Organ Transplantation recipients have elevated cancer incidence. Estimates of absolute cancer risk after Transplantation can inform prevention and screening. METHODS The Transplant Cancer Match Study links the US Transplantation registry with 14 state/regional cancer registries. The authors used nonparametric competing risk methods to estimate the cumulative incidence of cancer after Transplantation for 2 periods (1987-1999 and 2000-2008). For recipients from 2000 to 2008, the 5-year cumulative incidence, stratified by Organ, sex, and age at Transplantation, was estimated for 6 preventable or screen-detectable cancers. For comparison, the 5-year cumulative incidence was calculated for the same cancers in the general population at representative ages using Surveillance, Epidemiology, and End Results data. RESULTS Among 164,156 recipients, 8520 incident cancers were identified. The absolute cancer risk was slightly higher for recipients during the period from 2000 to 2008 than during the period from 1987 to 1999 (5-year cumulative incidence: 4.4% vs 4.2%; P = .006); this difference arose from the decreasing risk of competing events (5-year cumulative incidence of death, graft failure, or reTransplantation: 26.6% vs 31.9%; P 50 years; range, 0.36%-2.22%). For recipients aged >50 years, the 5-year cumulative incidence was higher for colorectal cancer (range, 0.33%-1.94%) than for the general population at the recommended screening age (aged 50 years: range, 0.25%-0.33%). For recipients aged >50 years, the 5-year cumulative incidence was high for lung cancer among thoracic Organ recipients (range, 1.16%-3.87%) and for kidney cancer among kidney recipients (range, 0.53%-0.84%). The 5-year cumulative incidence for prostate cancer and breast cancer was similar or lower in Transplantation recipients than at the recommended ages of screening in the general population. CONCLUSIONS Subgroups of Transplantation recipients have a high absolute risk of some cancers and may benefit from targeted prevention or screening. Cancer 2013;119:2300–2308. © 2013 American Cancer Society.
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skin cancers associated with hiv infection and Solid Organ Transplantation among elderly adults
International Journal of Cancer, 2010Co-Authors: Emilie Lanoy, Dominique Costagliola, Eric A EngelsAbstract:Immunosuppression may be etiologic for some skin cancers. We investigated the impact of human immunodeficiency virus (HIV) infection and Solid Organ Transplantation on skin cancer risk. We conducted a population-based case-control study among elderly U.S. adults (non-Hispanic whites, age 67 years or older), using Surveillance, Epidemiology, and End Results (SEER) Medicare linked data. The study comprised 29,926 skin cancer cases (excluding basal cell and squamous cell carcinomas) and 119,704 controls, frequency-matched by gender, age, and calendar year (1987–2002). Medicare claims identified Solid Organ Transplantation or HIV infection before cancer diagnosis/control selection. As negative controls, we evaluated other medical conditions (e.g., hypertension, depression) and cancers (breast, colon, prostate) not linked to immunosuppression. Odds ratios (ORs) compared prevalence in cases and controls, adjusted for matching factors and number of prior physician claims. Risks of Kaposi sarcoma (N=602) and cutaneous non-Hodgkin lymphoma (N=1,836) were increased with Solid Organ Transplantation (OR [95%CI]: 11.06 [5.27–23.23] and 2.27 [1.00–5.15], respectively) and HIV infection (21.58 [11.94–38.99] and 2.41 [1.05–5.52], respectively). Solid Organ Transplantation was also associated with increased risks of Merkel cell carcinoma (N=1286; OR [95%CI] 4.95 [2.62–9.34]) and other cutaneous sarcomas (N=972; 4.19 [1.83–9.56]). Solid Organ Transplantation was non-significantly associated with melanoma (N=23,974; (OR 1.36 [95%CI 0.98–1.88]). Null or weak associations were observed for negative control medical conditions and cancers. Solid Organ Transplantation and HIV infection were followed by increased risk for some skin cancer subtypes among elderly adults. These results highlight the potential role of immunity in development of skin cancers.
Marcella Franquesa - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells in Solid Organ Transplantation misot fourth meeting lessons learned from first clinical trials
Transplantation, 2013Co-Authors: Marcella Franquesa, Martin J. Hoogduijn, Elke Eggenhofer, Marlies E.j. Reinders, A U Engela, F Mensah, J Torras, Antonello Pileggi, Cees Van Kooten, Bernard P MahonAbstract:textabstractThe Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem cells as a therapeutic agent in Solid Organ Transplantation and emphasizes the issues (proper timing, concomitant immunossupression, source and immunogenicity of mesenchymal stem cells, and oncogenicity) that have been addressed and will be followed up by the MiSOT Consortium in future studies.
Jay A Fishman - One of the best experts on this subject based on the ideXlab platform.
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infectious complications of antilymphocyte therapies in Solid Organ Transplantation
Clinical Infectious Diseases, 2009Co-Authors: Nicolas C Issa, Jay A FishmanAbstract:: Antilymphocyte therapies are widely used for immunosuppression in Solid Organ Transplantation. These agents have varied mechanisms of action, with resulting differences in the intensity and duration of immunosuppression and in associated infectious complications. Induction therapy with antithymocyte globulins is associated with a greater incidence of cytomegalovirus, Epstein-Barr virus, and BK polyomavirus infections, compared with therapy with interleukin (IL)-2a receptor antagonists. However, long-term experience with the IL-2a receptor antagonists is lacking. By contrast, the treatment of graft rejection with T cell-depleting antibodies is associated with an increased risk of opportunistic infections. This is likely a reflection of the intensification of immunosuppression in the treatment of graft rejection and, often, a failure to link the use of antilymphocyte agents to prophylaxis for infection. The use of T cell-depleting agents, especially in the treatment of acute graft rejection, must be linked to monitoring and risk-adjusted prophylaxis for Pneumocystis, other fungi, Epstein-Barr virus, BK polyomavirus, and cytomegalovirus infection.
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disparities in Solid Organ Transplantation for ethnic minorities facts and solutions
American Journal of Transplantation, 2006Co-Authors: Robert S D Higgins, Jay A FishmanAbstract:The Diversity and Minority Affairs Committee of the American Society of Transplantation (AST) convened a symposium to examine Organ Transplantation in underserved and minority populations. The goals of the meeting included ‘benchmarking’ of Solid Organ Transplantation among minority populations, review of the epidemiology of end-Organ damage, exploration of barriers to Transplantation services and development of approaches to eliminate disparities. Participants noted that minority populations were more likely to be adversely affected by limited preventive medical care, lack of counseling regarding transplant options, and delays in transplant referrals for Organ Transplantation. These features largely reflect economic disadvantage as well as the reduced presence of minority professionals with training in transplant-related specialties. Participants in the conference noted that recent changes in Organ allocation policies had improved access to minority individuals once listed for renal Transplantation. Similar advances will be needed for other Organs to address inequities in pretransplant care and underrepresentation of minorities among transplant professionals. The biologic basis of differences in transplant outcomes for minority recipients has not been adequately studied. Research funds must be targeted to address biologic mechanisms underlying disparate transplant outcomes including the impacts of environment, education, poverty and lifestyle choices.
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canadian society of Transplantation consensus workshop on cytomegalovirus management in Solid Organ Transplantation final report
American Journal of Transplantation, 2005Co-Authors: Jutta K Preiksaitis, Daniel C. Brennan, Jay A Fishman, Upton AllenAbstract:: The Canadian Society of Transplantation sponsored a Cytomegalovirus (CMV) Consensus Working Group that met on March 19, 2003. The objectives of this group were to determine the current burden of CMV-associated disease in the setting of Solid Organ Transplantation in Canada, make recommendations regarding optimal strategies for the diagnosis, treatment and prevention of CMV infection and disease, highlight gaps in knowledge and outline priorities for research and other initiatives that might further reduce the burden of CMV-associated effects in this setting. This report summarizes the recommendations of the working group including ratings of the strength of evidence supporting the recommendations.
Martin J. Hoogduijn - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells in Solid Organ Transplantation misot fourth meeting lessons learned from first clinical trials
Transplantation, 2013Co-Authors: Marcella Franquesa, Martin J. Hoogduijn, Elke Eggenhofer, Marlies E.j. Reinders, A U Engela, F Mensah, J Torras, Antonello Pileggi, Cees Van Kooten, Bernard P MahonAbstract:textabstractThe Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem cells as a therapeutic agent in Solid Organ Transplantation and emphasizes the issues (proper timing, concomitant immunossupression, source and immunogenicity of mesenchymal stem cells, and oncogenicity) that have been addressed and will be followed up by the MiSOT Consortium in future studies.
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Advancement of mesenchymal stem cell therapy in Solid Organ Transplantation (MISOT)
Transplantation, 2010Co-Authors: Martin J. Hoogduijn, Felix C. Popp, Anja U. Grohnert, Meindert J. Crop, Marieke Van Rhijn, Ajda T. Rowshani, Elke Eggenhofer, Philipp Renner, Marlies E.j. Reinders, Ton J. RabelinkAbstract:There is evolving interest in the use of mesenchymal stem cells (MSC) in Solid Organ Transplantation. Pre-clinical Transplantation models show efficacy of MSC in prolonging graft survival and a number of clinical studies are planned or underway. At a recent meeting of the MISOT consortium (MSC In Solid Organ Transplantation) the advances of these studies were evaluated and mechanisms underlying the potential effects of MSC discussed. Continued discussion is required for definition of safety and eventually efficacy endpoints for MSC therapy in Solid Organ Transplantation.