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T-cells, bone marrow transplant

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https://www.readbyqxmd.com/read/29155317/treosulfan-fludarabine-conditioning-for-hsct-in-children-with-primary-immunodeficiency-uk-experience
#1
Mary A Slatter, Kanchan Rao, Intan Juliana Abd Hamid, Zohreh Nademi, Robert Chiesa, Reem Elfeky, Mark S Pearce, Persis Amrolia, Austen Worth, Terence Flood, Mario Abinun, Sophie Hambleton, Waseem Qasim, Hubert B Gaspar, Andrew J Cant, Andrew R Gennery, Paul Veys
We previously published results of 70 children who received treosulfan with cyclophosphamide (30) or fludarabine (40) before haematopoietic stem cell transplantation (HSCT) for Primary Immunodeficiency (PID). Toxicity was lower and T cell chimerism better in those receiving fludarabine, but numbers were relatively small and follow-up short. We now report outcome of 160 children who received homogeneous conditioning with treosulfan, fludarabine mostly with alemtuzumab (n=124). Median age at transplant was 1...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29155316/influence-of-age-on-acute-and-chronic-gvhd-in-children-receiving-hla-identical-sibling-bmt-for-acute-leukemia-implications-for-prophylaxis
#2
Muna Qayed, Tao Wang, Michael T Hemmer, Stephen Spellman, Mukta Arora, Daniel Couriel, Amin Alousi, Joseph Pidala, Hisham Abdel-Azim, Mahmoud Aljuf, Mouhab Ayas, Menachem Bitan, Mitchell Cairo, Sung Won Choi, Christopher Dandoy, David Delgado, Robert Peter Gale, Gregory Hale, Haydar Frangoul, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Leslie Lehman, John Levine, Margaret MacMillan, David I Marks, Taiga Nishihori, Richard F Olsson, Peiman Hematti, Olov Ringden, Ayman Saad, Prakash Satwani, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Shalini Shenoy, Edmund K Waller, Lolie Yu, Mary M Horowitz, John Horan
Relapse remains the major cause of mortality post hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research suggests that reducing the intensity of calcineurin inhibitor based graft versus host disease (GVHD) prophylaxis may be an effective strategy in abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29152660/therapeutic-effects-of-stat3-inhibition-by-nifuroxazide-on-murine-acute-graft-graft-vs-host-disease-old-drug-new-use
#3
Huijie Jia, Jing Cui, Xiaolong Jia, Jingjing Zhao, Yuchen Feng, Peijuan Zhao, Dan Zang, Jian Yu, Tiesuo Zhao, Hui Wang, Kailin Xu
Graft‑vs.‑host disease (GvHD) is a major and lethal complication of allogeneic bone marrow transplantation (allo‑BMT). Although great development has been made, the treatment progress of this disorder is slow. Research has illustrated that STAT3 was critical for T cell alloactivation in GvHD. In the present study, the authors hypothesized that nifuroxazide, as the STAT3 inhibitor, treatment may attenuate the development of acute GvHD (aGvHD). The results demonstrated that nifuroxazide suppressed the development of aGvHD and significantly delayed aGvHD‑induced lethality...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29152615/scid-pigs-an-emerging-large-animal-nk-model
#4
Ellis J Powell, Joan E Cunnick, Christopher K Tuggle
Severe Combined ImmunoDeficiency (SCID) is defined as the lack or impairment of an adaptive immune system. Although SCID phenotypes are characteristically absent of T and B cells, many such SCID cellular profiles include the presence of NK cells. In human SCID patients, functional NK cells may impact the engraftment success of life saving procedures such as bone marrow transplantation. However, in animal models, a T cell-, B cell-, NK cell+ environment provides a valuable tool for asking specific questions about the extent of the innate immune system function as well as emerging NK targeted therapies against cancer...
2017: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/29152068/age-associated-and-therapy-induced-alterations-in-the-cellular-microenvironment-of-experimental-gliomas
#5
Hannah Schneider, Birthe Lohmann, Hans-Georg Wirsching, Kathy Hasenbach, Elisabeth J Rushing, Karl Frei, Martin Pruschy, Ghazaleh Tabatabai, Michael Weller
The poor prognosis associated with advanced age in patients with glioblastoma remains poorly understood. Glioblastoma in the elderly has been particularly associated with vascular endothelial growth factor (VEGF)-dependent angiogenesis, and early uncontrolled studies suggested that the anti-angiogenic agent bevacizumab (BEV), an antibody to VEGF, might be preferentially active in this patient population. Accordingly, we explored host age-dependent differences in survival and benefit from radiotherapy (RT) or BEV in syngeneic mouse glioma models...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147589/%C3%AE-%C3%AE-t-cell-acute-lymphoblastic-leukemia-lymphoma-discussion-of-two-pediatric-cases-and-its-distinction-from-other-mature-%C3%AE-%C3%AE-t-cell-malignancies
#6
Eric X Wei, Vasiliki Leventaki, John K Choi, Susana C Raimondi, Elizabeth M Azzato, Sheila A Shurtleff, Menchu G Ong, Diana M Veillon, James D Cotelingam, Rodney E Shackelford
Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29144072/relapse-and-cytogenetic-evolution-in-myeloid-neoplasms
#7
Natalie Ertz-Archambault, Katalin Kelemen
Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms...
December 2017: Panminerva Medica
https://www.readbyqxmd.com/read/29141868/geographic-clonal-tracking-in-macaques-provides-insights-into-hspc-migration-and-differentiation
#8
Chuanfeng Wu, Diego A Espinoza, Samson J Koelle, E Lake Potter, Rong Lu, Brian Li, Di Yang, Xing Fan, Robert E Donahue, Mario Roederer, Cynthia E Dunbar
The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs with genetic barcodes, allowing clonal tracking over time and space after transplantation. We found marked geographic segregation of CD34(+) HSPCs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at different BM sites over subsequent months to years...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29132870/mtor-inhibitor-rapamycin-induce-polymorphonuclear-myeloid-derived-suppressor-cells-mobilization-and-function-in-protecting-against-acute-graft-versus-host-disease-after-bone-marrow-transplantation
#9
Yu Lin, Binsheng Wang, Wei Shan, Yamin Tan, Jingjing Feng, Lin Xu, Limengmeng Wang, Biqing Han, Mingming Zhang, Jian Yu, Xiaohong Yu, He Huang
The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) has been shown to be an effective immunosuppressor in the management of acute graft-versus-host disease (aGVHD) after bone marrow transplantation. Myeloid-derived suppressor cells (MDSCs) also have a protective effect in aGVHD regulation. However, the relationship between RAPA and MDSCs in aGVHD models is unclear. Meanwhile, the effect of RAPA on different subgroups of MDSCs is also less well described. In this study, we demonstrate that in vivo administration of RAPA results in the expansion and functional enhancement of polymorphonuclear MDSCs (PMN-MDSCs) in a murine model of aGVHD...
November 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29131156/impact-of-choice-timing-sequence-and-combination-of-broad-spectrum-antibiotics-on-the-outcome-of-allogeneic-haematopoietic-stem-cell-transplantation
#10
F Farowski, V Bücker, J J Vehreschild, L Biehl, R Cruz-Aguilar, C Scheid, U Holtick, N Jazmati, H Wisplinghoff, O A Cornely, M J G T Vehreschild
Recent data link the incidence of intestinal GvHD (iGvHD) after allogeneic haematopoietic stem cell transplantation (aSCT) to exposure with piperacillin-tazobactam or imipenem-cilastatin. To assess relevance of timing, duration, sequence and combination of antibiotic treatment in this setting, we applied a time-dependent model to our aSCT cohort. Patients from the prospective Cologne Cohort of Neutropenic Patients (CoCoNut) undergoing aSCT from January 2007 to April 2013 were included into a time-dependent multivariate Cox proportional hazards regression model with backward-stepwise selection...
November 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29131154/impact-of-hla-g-polymorphism-on-the-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-for-metastatic-renal-cell-carcinoma
#11
R Crocchiolo, O Ringden, J-O Bay, D Blaise, B Omasic, B Mazzi, C Picard, S Trinca, L Barkholt, J Peccatori, S Gregori, G Amodio, K Fleischhauer, F Ciceri, M Bregni
Renal cell carcinoma (RCC) is particularly sensitive to immune intervention. HLA-G, a non-classical HLA class I molecule with immunomodulatory properties, has been studied with regard to outcome after hematopoietic stem cell transplantation (HSCT), in particular the 14 bp insertion/deletion polymorphism in the 3' untranslated region. Here we analyzed n=56 patients affected by metastatic RCC who received an allogeneic HSCT between 1998 and 2006 in Milano, Marseille, Clermont-Ferrand and Stockholm. The 14 bp polymorphism was analyzed in correlation with overall survival (OS), PFS, acute and chronic GvHD...
November 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29131150/neurologic-complications-after-allogeneic-hematopoietic-stem-cell-transplantation-risk-factors-and-impact
#12
M R Dowling, S Li, B R Dey, S L McAfee, H R Hock, T R Spitzer, Y-B Chen, K K Ballen
Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy...
November 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29128556/pro-140-monoclonal-antibody-to-ccr5-prevents-acute-xenogeneic-graft-versus-host-disease-in-nod-scid-il-2ry-null-mice
#13
Denis R Burger, Yvonne Parker, Kathryn Guinta, Daniel Lindner
Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication of hematopoietic stem cell transplantation (HSCT). Humanized mouse models of xenogeneic-GvHD are important tools used to study the human immune response in vivo. Here we used NOD-scid IL-2Ry(null) mice (NSG) transplanted with human bone marrow stem cells to evaluate the role of immune cell engraftment in the production of acute GvHD. PRO 140, a humanized monoclonal antibody targeting the chemokine receptor, CCR5, was used to evaluate its influence on bone marrow cell engraftment and modulation of acute GvHD...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29125102/role-of-methylprednisolone-in-treatment-of-spinal-cord-injured-with-bone-marrow-mesenchymal-stem-cells-transplantation-in-rats-and-its-effect-on-the-expressions-of-tumor-necrosis-factor-%C3%AE-and-interleukin-1%C3%AE
#14
Xin-Ming Yang, Yao-Yu Cheng, Zhen-Liang Zhang, Cong Kang
Objective To investigate the role of methylprednisolone (MP) in treatment of spinal cord injured (SCI) with bone marrow mesenchymal stem cells (BMSCs) transplantation in rats and its effect on the expressions of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) at the local tissues.Methods Forty male Sprague-Dawley(SD) rats were used to establish the models of SCI according to the modified Allen's contusion method and then divided into four groups (n=10 in each group) by using random numbers table:MP group,BMSCs group,BMSCs+MP group,and control group...
October 30, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29107583/outcomes-of-patients-with-relapsed-core-binding-factor-positive-acute-myeloid-leukemia
#15
Maliha Khan, Jorge Cortes, Wei Qiao, Mohanad A Alzubaidi, Sherry A Pierce, Farhad Ravandi, Hagop M Kantarjian, Gautam Borthakur
PURPOSE: To determine the factors associated with outcomes in patients with core binding factor acute myeloid leukemia (CBF-AML) in first relapse. MATERIAL AND METHODS: We conducted a retrospective analysis of 92 patients with CBF-AML in first relapse who presented to our institution from 1990-2014. Clinical and demographic parameters were included in univariate and multivariate Cox proportional hazards regression model to predict overall survival. RESULTS: Among the 92 relapsed patients, 60 (65%) patients had inv (16) and 32 (35%) had t (8;21)...
September 25, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29105189/cyclophosphamide-induced-tolerance-in-kidney-transplantation-avoids-long-term-immunosuppressive-therapy
#16
REVIEW
Ario Takeuchi, Koji Kato, Koichi Akashi, Masatoshi Eto
There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of T cells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation...
November 3, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29102721/cellular-immunotherapy-for-haematological-malignancies-beyond-bone-marrow-transplant
#17
REVIEW
Melita Cirillo, Peter Tan, Marian Sturm, Catherine Cole
Immunotherapy has changed treatment practices for many haematological malignancies. Despite the current era of targeted therapy, chemotherapy remains the backbone of treatment for many haematological malignancies, especially in acute leukaemia, where relapse remains the major cause of mortality. Application of novel immunotherapies in haematology attempts to harness the killing power of the immune system against leukaemia and lymphoma. Cellular immunotherapy is evolving rapidly for high risk haematological disorders...
November 1, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29101827/differential-t-cell-subsets-and-cytokine-profile-between-steady-state-and-g-csf-primed-bone-marrow-and-its-association-with-graft-versus-host-disease
#18
Eucario León-Rodríguez, Monica M Rivera-Franco, Diana Gómez-Martín, Jorge Romo-Tena, Guillermo Juárez-Vega, Javier Merayo-Chalico, Jorge Alcocer-Varela
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). At our Institution, patients transplanted using G-CSF-primed bone marrow (G-BM), have a lower incidence of GVHD when compared to other sources. The objective of this study was to analyze and compare T cell subsets and cytokines in donor G-BM and steady-state BM (SS-BM). A prospective study was performed in 48 donor samples. Mononuclear cells were isolated by gradient density. T cell subsets and cytokine production in supernatants were analyzed by multiparametric flow cytometry...
November 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29100944/regulatory-dendritic-cells-for-promotion-of-liver-transplant-operational-tolerance-rationale-for-a-clinical-trial-and-accompanying-mechanistic-studies
#19
REVIEW
Angus W Thomson, Abhinav Humar, Fadi G Lakkis, Diana M Metes
Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8(+) memory T cell responses in the early post-transplant period...
October 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/29099650/new-insights-into-graft-versus-host-disease-and-graft-rejection
#20
Eric Perkey, Ivan Maillard
Allogeneic transplantation of foreign organs or tissues has lifesaving potential, but can lead to serious complications. After solid organ transplantation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. After bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. T cells are central mediators of alloimmune complications and the target of most existing therapeutic interventions...
November 3, 2017: Annual Review of Pathology
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