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Transplantation Induction

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https://www.readbyqxmd.com/read/27913522/role-of-stem-cell-transplant-and-maintenance-therapy-in-plasma-cell-disorders
#1
Philip L McCarthy, Sarah A Holstein
Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#2
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#3
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911488/hepatocellular-carcinoma-as-an-emerging-morbidity-in-the-thalassemia-syndromes-a-comprehensive-review
#4
REVIEW
Hassan M Moukhadder, Racha Halawi, Maria Domenica Cappellini, Ali T Taher
The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27909438/donor-specific-regulatory-t-cells-acquired-from-tolerant-mice-bearing-cardiac-allograft-promote-mixed-chimerism-and-prolong-intestinal-allograft-survival
#5
Xiao-Fei Shen, Jin-Peng Jiang, Jian-Jun Yang, Wei-Zhong Wang, Wen-Xian Guan, Jun-Feng Du
The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation (SBT), which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts, such as skin, kidney, and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27906827/cross-talk-between-t-and-b-cells-in-the-germinal-center-following-transplantation
#6
Jean Kwun, Miriam Manook, Eugenia Page, Christopher Burghuber, Jungjoo Hong, Stuart J Knechtle
Cross-talk between B and T cells in transplantation is increasingly recognized as being important in the alloimmune response. T cell activation of B cells occurs by a 3-stage pathway, culminating with costimulation signals. We review the distinct T cell subtypes required for B cell activation, and discuss the formation of the Germinal Center (GC) after transplantation, with particular reference to the repopulation of the GC following depletional induction, and the subsequent effect of immunosuppressive manipulation of T-B cell interactions...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27906439/in-vitro-neural-differentiation-of-bone-marrow-stromal-cells-induced-by-hepatocyte-growth-factor-and-glial-cell-derived-neurotrophic-factor
#7
Q Ma, M Cai, J-W Shang, J Yang, X-Y Gu, W-B Liu, Q Yang
OBJECTIVE: Bone marrow stromal cells (BMSCs) have great potential for cell-based transplantation therapy in treating neurological disease. However, the best combination of various trophic factors to produce full neural differentiation of BMSCs was still unclear. In our study, we aimed to investigate the neural differentiation capacity of rat BMSCs induced by growth factors including hepatocyte growth factor (HGF) and glial cell-derived neurotrophic factor (GDNF). MATERIALS AND METHODS:   Cell counting kit-8 (CCK-8) assay, BrdU cell proliferation assay and flow cytometry were implemented to evaluate whether GDNF and HGF had positive effects on the proliferation of BMSCs...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27904491/intravenous-transplantation-of-mouse-embryonic-stem-cells-attenuates-demyelination-in-an-icr-outbred-mouse-model-of-demyelinating-diseases
#8
Kidsadagon Pringproa, Anucha Sathanawongs, Chananthida Khamphilai, Sarocha Sukkarinprom, Apichart Oranratnachai
Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intravenous cell transplantation in the present developed mouse model...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27900974/disseminated-mycobacteria-chelonae-infection-in-a-kidney-pancreas-transplant-recipient-a-case-report-and-review-of-the-literature
#9
Shafi Malik, Ananda Ghosh, Shahid Husain
A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP) transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg)...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27898463/transplantation-tolerance-after-allograft-rejection
#10
Michelle L Miller, Maria-Luisa Alegre, Anita S Chong
PURPOSE OF REVIEW: Although elusive for many decades, transplantation tolerance can now be achieved in the clinic. This has prompted follow-up investigations into its stability and longevity, as well as into barriers to its induction, which include memory T and B cells. RECENT FINDINGS: Clinical observations reveal that transplantation tolerance can be induced in adult recipients and that even episodes of acute rejection do not preclude successful weaning from immunosuppression to reveal tolerance...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27893836/prognostic-value-of-serum-free-light-chains-measurements-in-multiple-myeloma-patients
#11
José Luis García de Veas Silva, Carmen Bermudo Guitarte, Paloma Menéndez Valladares, Johanna Carolina Rojas Noboa, Krysta Kestler, Rafael Duro Millán
BACKGROUND: The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment...
2016: PloS One
https://www.readbyqxmd.com/read/27891557/exogenous-expression-of-nt-3-and-trkc-genes-in-bone-marrow-stromal-cells-elevated-the-survival-rate-of-the-cells-in-the-course-of-neural-differentiation
#12
Houri Edalat, Zahra Hajebrahimi, Vahid Pirhajati, Mahmoud Tavallaei, Mansoureh Movahedin, Seyed Javad Mowla
Bone marrow stromal cells (BMSCs) are attractive cellular sources for cell therapy of many diseases, specifically neurodegenerative ones. The potential capability of BMSCs could be further augmented by enhancing their neuroprotective property, differentiation potential, and survival rate subsequent to transplantation. Therefore, a concurrent upregulation of neurotrophin-3 (NT-3) and its high affinity receptor, tyrosin kinase C (TrkC), was utilized in our study. BMSCs were cotransfected with pDsRed1-N1-NT-3 and pCMX-TrkC plasmids before induction of neural differentiation...
November 28, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27890698/clementine-juice-has-the-potential-for-drug-interactions-in-vitro-comparison-with-grapefruit-and-mandarin-juice
#13
Dirk Theile, Nicolas Hohmann, Dominik Kiemel, Giuseppe Gattuso, Davide Barreca, Gerd Mikus, Walter Emil Haefeli, Vedat Schwenger, Johanna Weiss
Adverse drug interactions due to grapefruit juice are well known prompting warnings even in drug labels. Similar issues have not been reported for clementines and available data is scarce, despite of genetic descent. We observed substantially increased tacrolimus trough concentrations in a renal transplant patient consuming high clementine amounts and, thus, scrutinised the effects of clementine juice on drug metabolism and drug transporters in vitro and compared it to the effects of mandarin and grapefruit juice...
November 24, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27890428/vancomycin-resistant-enterococcus-colonization-and-bacteremia-and-hematopoietic-stem-cell-transplantation-outcomes
#14
Clyde D Ford, Michaela A Gazdik, Bert K Lopansri, Brandon Webb, Birgitta Mitchell, Jana Coombs, Daanish Hoda, Finn Bo Petersen
The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms...
November 23, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27889929/twenty-eight-years-of-intestinal-transplantation-in-paris-experience-of-the-oldest-european-centre
#15
F Lacaille, S Irtan, L Dupic, C Talbotec, F Lesage, V Colomb, N Salvi, F Moulin, F Sauvat, Y Aigrain, Y Revillon, O Goulet, C Chardot
AIM: Our aim is to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. METHODS: After a period (1987-90) of 9 isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver-small bowel, 4 multivisceral (3 with kidneys), 1 modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34) and others (1)...
November 27, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27888768/multiple-myeloma-treatment-at-relapse-after-autologous-stem-cell-transplantation-a-practical-analysis
#16
REVIEW
F Malard, J L Harousseau, M Mohty
Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse...
November 15, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27888576/total-recall-can-we-reshape-t-cell-memory-by-lymphoablation
#17
Michael Nicosia, Anna Valujskikh
Despite recent advances in immunosuppression, donor-reactive memory T cells remain a serious threat to successful organ transplantation. To alleviate damaging effects of preexisting immunologic memory, lymphoablative induction therapies are used as a part of standard care in sensitized recipients. However, there is accumulating evidence that memory T cells have advantages over their naïve counterparts in surviving depletion and expanding under lymphopenic conditions. This may at least partially explain the inability of existing lymphoablative strategies to improve long term allograft outcome in sensitized recipients, despite well-documented decrease in the frequency of early acute rejection episodes...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27888093/randomized-trial-of-ratg-daclizumab-vs-ratg-alemtuzumab-as-dual-induction-therapy-in-renal-transplantation-results-at-8-years-of-follow-up
#18
Gaetano Ciancio, Jeffrey J Gaynor, Giselle Guerra, Junichiro Sageshima, David Roth, Linda Chen, Warren Kupin, Adela Mattiazzi, Lissett Tueros, Sandra Flores, Lois Hanson, Phillip Ruiz, Rodrigo Vianna, George W Burke
Our goal in using dual induction therapy is to bring the kidney transplant recipient closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state. Here, we report long-term results of a prospective randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs. (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus dosing, EC-MPS, and early corticosteroid withdrawal. Lower EC-MPS dosing was targeted in Group II to avoid severe leukopenia...
November 22, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27879593/triptolide-reduces-the-required-dose-of-tacrolimus-by-attenuating-inflammation-enhancing-immunosuppression-and-increasing-donor-chimerism-in-a-heterotopic-hindlimb-transplantation-model
#19
Chuan Gu, Fei Liu, Xusong Luo, Xianyu Zhou, Jun Yang, L Scott Levin
BACKGROUND: Induction of tolerance and minimizing the toxicity of immunosuppression are two fundamental goals in vascularized composite allotransplantation. Accumulating data indicate that triptolide is an agent that may have the capacity to suppress inflammation and immunologic rejection. METHODS: A heterotopic hindlimb allotransplantation model from Brown Norway to Lewis rats was established and treated with different doses of tacrolimus combined with or without triptolide...
December 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27879269/basophils-promote-tumor-rejection-via-chemotaxis-and-infiltration-of-cd8-t-cells
#20
Ibrahim M Sektioglu, Rafael Carretero, Nadja Bulbuc, Tobias Bald, Thomas Tüting, Alexander Y Rudensky, Günter J Hämmerling
Elevated numbers of regulatory T-cells (Tregs) in patient tumors are known to inhibit efficient anti-tumor T-cell responses. To study the mechanisms controlling tumor rejection, we assessed different mouse models for Treg depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8+ T cell-dependent way. In contrast, about 90% Treg depletion obtained in BAC transgenic Foxp3.LuciDTR4 mice failed to induce complete rejection of HCmel12 melanomas, demonstrating that residual Tregs were able to control CD8+ T cell responses against the tumor...
November 22, 2016: Cancer Research
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