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tolerance in transplantation

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https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#1
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28529646/peptide-vaccination-in-the-presence-of-adjuvants-in-patients-after-hematopoietic-stem-cell-transplantation-with-cd4-t-cell-reconstitution-elicits-consistent-cd8-t-cell-responses
#2
Michael Schmitt, Anita Schmitt, Markus Wiesneth, Angela Hückelhoven, Zeguang Wu, Jürgen Kuball, Lei Wang, Peter Schauwecker, Susanne Hofmann, Marlies Götz, Birgit Michels, Birgit Maccari, Patrick Wuchter, Volker Eckstein, Thomas Mertens, Paul Schnitzler, Hartmut Döhner, Anthony D Ho, Donald W Bunjes, Peter Dreger, Hubert Schrezenmeier, Jochen Greiner
Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality. Therefore we developed and manufactured a novel vaccine and initiated a clinical phase I trial with a CMV phosphoprotein 65 (CMVpp65)-derived peptide. Methods: Ten patients after allogeneic stem cell transplantation received four vaccinations at a biweekly interval. All patients were monitored for CMVpp65 antigenemia...
2017: Theranostics
https://www.readbyqxmd.com/read/28529613/long-term-outcome-of-inflammatory-breast-cancer-compared-to-non-inflammatory-breast-cancer-in-the-setting-of-high-dose-chemotherapy-with-autologous-hematopoietic-cell-transplantation
#3
Yee Chung Cheng, Yushu Shi, Mei-Jie Zhang, Ruta Brazauskas, Michael T Hemmer, Michael R Bishop, Yago Nieto, Edward Stadtmauer, Lois Ayash, Robert Peter Gale, Hillard Lazarus, Leona Holmberg, Michael Lill, Richard F Olsson, Baldeep Mona Wirk, Mukta Arora, Parameswaran Hari, Naoto Ueno
Introduction: Inflammatory breast cancer (IBC) is a rare aggressive form of breast cancer. It is well known that the long-term survival and progression-free survival of IBC are worse than that of non-IBC. We report the long term outcomes of patients with IBC and non-IBC who had undergone high-dose chemotherapy (HDC) with autologous hematopoietic cell transplantation (AHCT). Methods: All 3387 patients with IBC or non-IBC who underwent HDC with AHCT between1990-2002 and registered with CIBMTR were included in this analysis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28527129/efficacy-and-safety-of-plerixafor-for-the-mobilization-collection-of-peripheral-hematopoietic-stem-cells-for-autologous-transplantation-in-japanese-patients-with-multiple-myeloma
#4
Masaki Ri, Kosei Matsue, Kazutaka Sunami, Chihiro Shimazaki, Akio Hayashi, Yoshinori Sunaga, Toru Sasaki, Kenshi Suzuki
To evaluate the efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells (HSCs) for autologous transplantation in Japanese patients with multiple myeloma (MM). In a randomized study, patients received G-CSF (filgrastim, 400 µg/m(2)/day) for 4 days prior to the first dose of plerixafor. Starting on Day 4 evening and for up to 4 days, patients received either plerixafor (240 µg/kg/day) + G-CSF group (PG group) or G-CSF alone (G group). Daily apheresis started on Day 5 for up to 4 days, or until ≥6 × 10(6) CD34+ cells/kg were collected...
May 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28524868/diabetes-associated-microbiota-in-fa-fa-rats-is-modified-by-roux-en-y-gastric-bypass
#5
Tulika Arora, Florian Seyfried, Neil G Docherty, Valentina Tremaroli, Carel W le Roux, Rosie Perkins, Fredrik Bäckhed
Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism...
May 19, 2017: ISME Journal
https://www.readbyqxmd.com/read/28523010/beneficial-soil-bacterium-pseudomonas-frederiksbergensis-os261-augments-salt-tolerance-and-promotes-red-pepper-plant-growth
#6
Poulami Chatterjee, Sandipan Samaddar, Rangasamy Anandham, Yeongyeong Kang, Kiyoon Kim, Gopal Selvakumar, Tongmin Sa
Soil salinity, being a part of natural ecosystems, is an increasing problem in agricultural soils throughout the world. Pseudomonas frederiksbergensis OS261 has already been proved to be an effective bio-inoculant for enhancing cold stress tolerance in plants, however, its effect on salt stress tolerance is unknown. The main aim of the present study was to elucidate P. frederiksbergensis OS261 mediated salt stress tolerance in red pepper. The plants were exposed to a salt stress using NaCl at the concentrations of 50, 100, and 150 mM after 12 days of transplantation, while plant growth and enzyme activity were estimated 50 days after sowing...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28522573/lenalidomide-melphalan-dexamethasone-in-newly-diagnosed-patients-with-al-amyloidosis-results-of-a-prospective-phase-2-study-with-long-term-follow-up
#7
Ute Hegenbart, Tilmann Bochtler, Axel Benner, Natalia Becker, Christoph Kimmich, Arnt V Kristen, Jörg Beimler, Ernst Hund, Markus Zorn, Anja Freiberger, Marianne Gawlik, Hartmut Goldschmidt, Dirk Hose, Anna Jauch, Anthony D Ho, Stefan O Schönland
Chemotherapy in light chain amyloidosis aims to normalize the involved free light chain in serum, which leads to an improvement or at least stabilization of organ function in most responding patients. We performed a prospective single center phase 2 trial with 50 untreated patients not eligible for high-dose treatment. The treatment schedule comprised 6 cycles of oral lenalidomide, melphalan and dexamethasone every 4 weeks. After 6 months complete remission was achieved in 9 patients (18%), very good partial remission in 16 (32%) and partial response in 9 (18%)...
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#8
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521904/make-immunological-peace-not-war-potential-applications-of-tolerogenic-dendritic-cells
#9
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we explore the powerful immunosuppressive properties of tolerogenic dendritic cells and discuss their potential to bring about lifelong tolerance in transplantation and autoimmune disease. We also highlight an exciting new development in the field of malaria diagnosis that could facilitate early detection of the disease.
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28518214/immune-monitoring-as-prerequisite-for-transplantation-tolerance-trials
#10
REVIEW
Katayoun Behnam Sani, Birgit Sawitzki
Ever since its first application in clinical medicine, scientists have urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been successfully utilized in a still small number of patients...
May 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28513004/effects-of-encapsulated-porcine-islets-on-glucose-and-c-peptide-concentrations-in-diabetic-nude-mice-6%C3%A2-months-after%C3%A2-intraperitoneal-transplantation
#11
Masuhiro Nishimura, Naho Iizuka, Yasutaka Fujita, Osamu Sawamoto, Shinichi Matsumoto
BACKGROUND: In patients with type 1 diabetes, allogeneic islet transplantation can provide normal HbA1c concentrations, but it requires immunosuppression. Transplanting encapsulated islets into the peritoneal cavity could reduce or eliminate the need for immunosuppression. One of the uncertain features of intraperitoneal islet transplantation is the difficulty of measuring C-peptide concentrations in peripheral blood, which is often used for the marker of islet function. We hypothesized that secreted C-peptide from intraperitoneally transplanted islets was mostly consumed in the peritoneal cavity, which resulted in low C-peptide concentrations in peripheral blood...
May 16, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28506071/fecal-microbiota-transplantation-in-recurrent-clostridium-difficile-infection-in-a-patient-with-concomitant-inflammatory-bowel-disease
#12
Marta Gravito-Soares, Elisa Gravito-Soares, Francisco Portela, Manuela Ferreira, Carlos Sofia
The use of fecal microbiota transplantation in recurrent Clostridium difficile infection and coexistent inflammatory bowel disease remains unclear. A 61-year-old man with ulcerative pancolitis was diagnosed with a third recurrence of Clostridium difficile infection, previously treated with metronidazole, vancomycin and fidaxomicin. Fecal microbiota transplantation of an unrelated healthy donor was performed by the lower route. After a twelve month follow-up, the patient remains asymptomatic without Clostridium difficile infection relapses or inflammatory bowel disease flare-ups...
May 16, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28505675/-anti-lymph-angiogenic-strategies-to-improve-corneal-graft-survival
#13
Felix Bock, Claus Cursiefen
Corneal transplantation (keratoplasty) is the most frequently performed form of transplantation worldwide. A rejection reaction against the transplant is the main complication occurring after transplantation in an already vascularized, so-called "high-risk" recipient eye. Our group has shown that clinically invisible lymphatic vessels play a crucial role in the induction of a rejection reaction against the corneal graft, and that anti-(lymph)angiogenic therapies in the mouse model of keratoplasty can significantly improve transplant survival...
May 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28503959/emerging-drugs-for-prevention-of-t-cell-mediated-rejection-in-liver-and-kidney-transplantation
#14
Tiffany Cl Wong, Chung-Mau Lo, James Yy Fung
Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection. Areas covered. In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed...
May 15, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28502526/long-term-preservation-of-eri-and-ailanthus-silkworms-using-frozen-gonads
#15
Hisayoshi Fukumori, Jung Lee, Tsuguru Fujii, Zenta Kajiura, Yutaka Banno
Cryopreservation of eri and ailanthus silkworms using frozen gonads was investigated. First, we evaluated the freeze tolerance of ovary and testis in the eri silkworm, which showed high tolerance. Mating between frozen ovary-transplanted females and frozen testis-transplanted males produced 163.0 eggs, yielding 105.7 larvae per moth. In a second experiment, we tested the use of the eri silkworm as a host insect for gonad transplantation from ailanthus silkworm donors. A high success ratio for laid and hatched eggs was demonstrated for ovary transplantation (97...
May 11, 2017: Cryobiology
https://www.readbyqxmd.com/read/28495642/feasibility-of-lenalidomide-therapy-for-persistent-chronic-lymphocytic-leukemia-after-allogeneic-transplantation
#16
Maria R Khouri, Elias J Jabbour, Alison M Gulbis, Francesco Turturro, Celina Ledesma, Martin Korbling, Barry I Samuels, Sairah Ahmed, Amin M Alousi, Stefan O Ciurea, David Marin, Krina K Patel, Uday R Popat, Carlos E Bueso-Ramos, Roland L Bassett, Issa F Khouri
In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90-100 days post alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily if tolerated in each patient...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28494654/new-formulations-of-tacrolimus-and-prevention-of-acute-and-chronic-rejections-in-adult-kidney-transplant-recipients
#17
Lionel Rostaing, Thomas Jouve, Paolo Malvezzi
BACKGROUND: As tolerance is not yet achievable, the kidney-transplanted-patients have to take on a daily-basis immunosuppressive drugs in order to avoid acute rejection-AR-. The cornerstone of immunosuppression relies on tacrolimus-therapy which is potentially nephrotoxic. RESEARCH DESIGN AND METHODS: We identified from the studies published in the recent years those who were reporting on AR in de novo kidney-transplant recipients under tacrolimus-based therapy, as well as those who reported on the attempt to minimize tacrolimus-therapy...
May 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28494646/a-randomized-study-comparing-stem-cell-transplantation-vs-conventional-therapy-for-low-and-intermediate-risk-myelodysplastic-syndrome-patients
#18
Zhengping Yu, Jiahua Ding, Aining Sun, Zheng Ge, Baoan Chen, Depei Wu
The treatment of myelodysplastic syndromes (MDS) involves improving patient survival and quality of life and decreasing the likelihood of progression to AML. Although the treatment outcomes of MDS remain unsatisfactory, few comparative studies have been performed comparing the outcomes of low-risk and intermediate-risk patients treated with supportive care and chemotherapeutics to those of patients treated with allo-HSCT. Therefore, we designed a clinical control study to compare the outcomes of supportive care and chemotherapeutics versus allo-HSCT treatment in MDS patients...
May 11, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28489338/regulatory-t-cells-promote-natural-killer-cell-education-in-mixed-chimeras
#19
Benedikt Mahr, Nina Pilat, Svenja Maschke, Nicolas Granofszky, Christoph Schwarz, Lukas Unger, Karin Hock, Andreas M Farkas, Christoph Klaus, Heinz Regele, Thomas Wekerle
Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in non-irradiated recipient mice conditioned with costimulation blockade and mTOR inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation (BMT) led to BM engraftment and persistent chimerism without Treg transfer, but failed to induce skin graft tolerance...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28488185/where-do-the-new-drugs-fit-in-for-relapsed-refractory-hodgkin-lymphoma
#20
REVIEW
Niloufer Khan, Alison J Moskowitz
The standard approach for relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) following frontline treatment failure is salvage therapy followed by consolidation with high-dose therapy and autologous stem cell transplant (HDT/ASCT). While this overall treatment paradigm has been in place for several decades, recent studies have aimed to improve the efficacy and tolerability of salvage therapies by incorporating newer drugs, such as brentuximab vedotin (BV) and checkpoint inhibitors. Following HDT/ASCT, survival is improved due to the availability of BV and the checkpoint inhibitors, nivolumab and pembrolizumab; however, for patients responding to checkpoint inhibition, the appropriate length of treatment and the role of allogeneic stem cell transplant are unclear...
May 9, 2017: Current Hematologic Malignancy Reports
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