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T-cells, bone marrow transplant

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https://www.readbyqxmd.com/read/28644773/mobilized-peripheral-blood-stem-cells-versus-unstimulated-bone-marrow-as-a-graft-source-for-t-cell-replete-haploidentical-donor-transplantation-using-post-transplant-cyclophosphamide
#1
Asad Bashey, Mei-Jie Zhang, Shannon R McCurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen
Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics...
June 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28628089/elevated-bone-marrow-eosinophil-count-is-associated-with-high-incidence-of-severe-acute-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#2
Y Shimomura, M Hara, H Hashimoto, T Ishikawa
Predicting severe acute GvHD (aGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging but critical. Mild aGvHD may have a favorable impact on relapse, whereas severe aGvHD is associated with poor outcomes. The aim of this study was to evaluate whether elevated eosinophil count in the bone marrow (BM) at 1 month after HSCT is associated with a high incidence of new and severe aGvHD. We enrolled 101 consecutive patients; median age was 50 years, and 50.5% patients were male. The median eosinophil concentration in BM at 1 month after HSCT was 1...
June 19, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28620068/x-box-binding-protein-1-dependent-plasma-cell-responses-limit-the-development-of-atherosclerosis
#3
Andrew P Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A Newland, Alison J Finigan, Leanne Masters, Christoph J Binder, Ziad Mallat
Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies and their importance in both humans and mouse models is still unclear. Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28619045/human-adipose-derived-mesenchymal-stem-cells-alleviate-obliterative-bronchiolitis-in-a-murine-model-via-ido
#4
Guoping Zheng, Guanguan Qiu, Menghua Ge, Jianping He, Lanfang Huang, Ping Chen, Wei Wang, Qi Xu, Yaoqin Hu, Qiang Shu, Jianguo Xu
BACKGROUND: Long-term survival of lung transplantation is hindered by the development of obliterative bronchiolitis (OB). Adipose-derived stem cells (ASCs) were documented to have more potent immunosuppressive ability than mesenchymal stem cells (MSCs) from bone marrow and placenta. The goal of our study is to evaluate the effect of repeated administration of ASCs on OB and the involvement of indoleamine 2,3-dioxygenase (IDO) mediating the protective effect of ASCs in a heterotopic tracheal transplantation (HTT) model...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28618138/expansion-of-umbilical-cord-blood-aldehyde-dehydrogenase-expressing-cells-generates-myeloid-progenitor-cells-that-stimulate-limb-revascularization
#5
David M Putman, Tyler T Cooper, Stephen E Sherman, Ayesh K Seneviratne, Mark Hewitt, Gillian I Bell, David A Hess
Uncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH(hi) cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDH(hi) cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (<0.5%) of these cells. Our goal was to generate a clinically-translatable, allogeneic cell population for vessel regenerative therapies, via ex vivo expansion of UCB ALDH(hi) cells without loss of pro-angiogenic potency...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#6
Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
BACKGROUND: Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. METHODS: To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice...
June 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28607915/engineering-cord-blood-to-improve-engraftment-after-cord-blood-transplant
#7
REVIEW
Rohtesh S Mehta, Hema Dave, Catherine M Bollard, Elizabeth J Shpall
Umbilical cord blood transplant (CBT) has traditionally been associated with slower engraftment of neutrophils, delayed immune reconstitution and consequently higher risk of infections as compared with peripheral blood progenitor cell (PBPC) or bone marrow (BM) transplants. This is primarily due to low numbers of total nucleated cells (TNCs) and the naive nature of CB immune cells. The use of double unit CB transplant (DCBT) increases the total cell dose in the graft, but it still does not produce as rapid engraftment as seen with PBPC or even BM transplants...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28606226/-expression-of-%C3%AE-integrin-family-members-in-children-with-t-cell-acute-lymphoblastic-leukemia
#8
Qing-Lin Kong, Xi-Zhou An, Xian-Min Guan, Yi-Mei Ma, Peng-Fei Li, Shao-Yan Liang, Yan-Ni Hu, Ying-Hui Cui, Jie Yu
OBJECTIVE: To study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance. METHODS: Quantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28605290/early-response-based-therapy-stratification-improves-survival-in-adult-early-thymic-precursor-acute-lymphoblastic-leukemia-a-group-for-research-on-adult-acute-lymphoblastic-leukemia-study
#9
Jonathan Bond, Carlos Graux, Ludovic Lhermitte, Diane Lara, Thomas Cluzeau, Thibaut Leguay, Agata Cieslak, Amélie Trinquand, Cedric Pastoret, Mohamed Belhocine, Salvatore Spicuglia, Véronique Lheritier, Stéphane Leprêtre, Xavier Thomas, Françoise Huguet, Norbert Ifrah, Hervé Dombret, Elizabeth Macintyre, Nicolas Boissel, Vahid Asnafi
Purpose Early thymic precursor (ETP) acute lymphoblastic leukemia (ALL) is an immunophenotypically defined subgroup of T-cell ALL (T-ALL) associated with high rates of intrinsic treatment resistance. Studies in children have shown that the negative prognostic impact of chemotherapy resistance is abrogated by the implementation of early response-based intensification strategies. Comparable data in adults are lacking. Patients and Methods We performed comprehensive clinicobiologic, genetic, and survival analyses of a large cohort of 213 adult patients with T-ALL, including 47 patients with ETP-ALL, treated in the GRAALL (Group for Research on Adult Acute Lymphoblastic Leukemia) -2003 and -2005 studies...
June 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28599679/evaluation-of-bone-marrow-mononuclear-cells-as-an-adjunct-therapy-to-minced-muscle-graft-for-the-treatment-of-volumetric-muscle-loss-injuries
#10
Stephen M Goldman, Beth E P Henderson, Benjamin T Corona
BACKGROUND: The delivery of alternative myogenic cell sources to enhance the efficacy of minced muscle grafts (MG) for the treatment of volumetric muscle loss (VML) injuries is a promising strategy to overcome the demand on muscle-derived donor tissue that currently limits the translation of this therapy. METHODS: Using a rat model of VML, bone marrow mononuclear cells (BMNCs) were evaluated for their ability to directly contribute to de novo muscle fiber regeneration by transplanting MG in a collagen carrier at a dose of 50% of the VML injury both with and without concomitant delivery of 5 million BMNCs derived via density gradient centrifugation from the bone marrow of a syngeneic green fluorescent protein (GFP)(+) donor...
June 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28596542/leukocyte-bim-deficiency-does-not-impact-atherogenesis-in-ldlr-mice-despite-a-pronounced-induction-of-autoimmune-inflammation
#11
Lieve Temmerman, Marijke M Westra, Ilze Bot, Bart J M van Vlijmen, Niek Van Bree, Martine Bot, Kim L L Habets, Tom G H Keulers, Johan van der Vlag, Thomas G Cotter, Theo J C van Berkel, Erik A L Biessen
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim (-/-) or wild type bone marrow transplanted ldlr (-/-) mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596376/cre-lox-studies-identify-resident-macrophages-as-the-major-source-of-circulating-coagulation-factor-xiii-a
#12
Cora M L Beckers, Kingsley R Simpson, Kathryn J Griffin, Jane M Brown, Lih T Cheah, Kerrie A Smith, Jean Vacher, Paul A Cordell, Mark T Kearney, Peter J Grant, Richard J Pease
OBJECTIVE: To establish the cellular source of plasma factor (F)XIII-A. APPROACH AND RESULTS: A novel mouse floxed for the F13a1 gene, FXIII-A(flox/flox) (Flox), was crossed with myeloid- and platelet-cre-expressing mice, and cellular FXIII-A mRNA expression and plasma and platelet FXIII-A levels were measured. The platelet factor 4-cre.Flox cross abolished platelet FXIII-A and reduced plasma FXIII-A to 23±3% (P<0.001). However, the effect of platelet factor 4-cre on plasma FXIII-A was exerted outside of the megakaryocyte lineage because plasma FXIII-A was not reduced in the Mpl(-/-) mouse, despite marked thrombocytopenia...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28593990/loss-of-asxl2-leads-to-myeloid-malignancies-in-mice
#13
Jianping Li, Fuhong He, Peng Zhang, Shi Chen, Hui Shi, Yanling Sun, Ying Guo, Hui Yang, Na Man, Sarah Greenblatt, Zhaomin Li, Zhengyu Guo, Yuan Zhou, Lan Wang, Lluis Morey, Sion Williams, Xi Chen, Qun-Tian Wang, Stephen D Nimer, Peng Yu, Qian-Fei Wang, Mingjiang Xu, Feng-Chun Yang
ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2(-/-) mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte-macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2(-/-) and Asxl2(+/-) BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28592067/-combination-of-pp242-and-dasatinib-suppresses-the-progression-of-acute-myeloid-leukemia-in-a-mouse-model
#14
Y H Qu, H T Liu, F C He
Objective: To establish the acute myeloid leukemia (AML) mouse model, and to preliminarily investigate the efficiency of dasatinib, a tryosine kinase inhibitor, and PP242, an inhibitor of PI3K/Akt/mTOR signaling pathway in the development of AML. Methods: The lineage(-) (Lin(-)) cells of C57BL/6J were transduced with retrovirus carrying MSCV-MLL-AF9-IRES-GFP fusion gene. The transduced cells were transplanted into lethally irradiated recipient mice to induce AML, and then the AML mouse model were established...
May 30, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28583547/major-histocompatibilty-complex-restricted-adaptive-immune-responses-to-ct26-colon-cancer-cell-line-in-mixed-allogeneic-chimera
#15
K W Lee, B Choi, Y M Kim, C W Cho, H Park, J I Moon, G-S Choi, J B Park, S J Kim
BACKGROUND: Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. METHODS: We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28583289/long-term-outcomes-after-standard-graft-versus-host-disease-prophylaxis-with-or-without-anti-human-t-lymphocyte-immunoglobulin-in-haemopoietic-cell-transplantation-from-matched-unrelated-donors-final-results-of-a-randomised-controlled-trial
#16
Jürgen Finke, Claudia Schmoor, Wolfgang Andreas Bethge, Hellmut Ottinger, Matthias Stelljes, Liisa Volin, Dominik Heim, Hartmut Bertz, Olga Grishina, Gerard Socie
BACKGROUND: Previously, we demonstrated that the addition of anti-human-T-lymphocyte immunoglobulin (ATLG) to standard ciclosporin and methotrexate prophylaxis reduced graft-versus-host disease (GvHD) in adult patients treated with allogeneic haemopoietic cell transplantation from matched unrelated donors without negatively affecting relapse and survival. Since reports on long-term results from randomised trials testing anti-thymocyte globulin are scarce, we performed an extended follow-up of the trial...
June 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28581470/low-egf-in-myeloablative-allotransplantation-association-with-severe-acute-gvhd-in-bmt-ctn-0402
#17
S G Holtan, L F Newell, C Cutler, M R Verneris, T E DeFor, J Wu, A Howard, M L MacMillan, J H Antin, B R Blazar, D J Weisdorf, A Panoskaltsis-Mortari
Epidermal growth factor (EGF) is a recently described biomarker of acute GvHD (aGvHD). Whether low plasma EGF prior to hematopoietic cell transplantation (HCT) predisposes to the development of aGvHD, or whether EGF levels fall because of severe aGvHD, is unknown. To evaluate this, we tested plasma samples collected at pre-HCT baseline, day +28 and day +100 during the course of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. We found that baseline EGF plasma concentrations were three-fold lower in HCT recipients compared to donors (24...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28581468/a-phase-i-ii-minor-histocompatibility-antigen-loaded-dendritic-cell-vaccination-trial-to-safely-improve-the-efficacy-of-donor-lymphocyte-infusions-in-myeloma
#18
L E Franssen, M W H Roeven, W Hobo, R Doorn, R Oostvogels, J H F Falkenburg, N W van de Donk, M G D Kester, H Fredrix, K Westinga, I Slaper-Cortenbach, E Spierings, M J Kersten, H Dolstra, T Mutis, N Schaap, H M Lokhorst
Allogeneic stem cell transplantation (allo-SCT) with or without donor lymphocyte infusions (DLI) is the only curative option for several hematological malignancies. Unfortunately, allo-SCT is often associated with GvHD, and patients often relapse. We therefore aim to improve the graft-versus-tumor effect, without increasing the risk of GvHD, by targeting hematopoietic lineage-restricted and tumor-associated minor histocompatibility antigens using peptide-loaded dendritic cell (DC) vaccinations. In the present multicenter study, we report the feasibility, safety and efficacy of this concept...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28581467/directionality-of-non-permissive-hla-dpb1-t-cell-epitope-group-mismatches-does-not-improve-clinical-risk-stratification-in-8-8-matched-unrelated-donor-hematopoietic-cell-transplantation
#19
K Fleischhauer, K W Ahn, H L Wang, L Zito, P Crivello, C Müller, M Verneris, B E Shaw, J Pidala, M Oudshorn, S J Lee, S R Spellman
In 8/8 HLA-matched unrelated donor (UD) hematopoietic cell transplants (HCT), HLA-DPB1 mismatches between alleles from different T-cell epitope (TCE) groups (non-permissive mismatches) are associated with significantly higher risks of mortality compared with those between alleles from the same TCE group (permissive mismatches); however, the relevance of mismatch directionality, that is (host vs graft (uni-directional HvG), graft vs host (uni-directional GvH) or both (bi-directional) in the non-permissive setting is unknown...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28581466/high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-primary-central-nervous-system-lymphoma-a-multi-centre-retrospective-analysis-from-the-united-kingdom
#20
S Kassam, E Chernucha, A O'Neill, C Hemmaway, T Cummins, S Montoto, A Lennard, G Adams, K Linton, P McKay, D Davies, C Rowntree, S Easdale, T A Eyre, R Marcus, K Cwynarski, C P Fox
The prognosis of patients with primary central nervous system lymphoma (PCNSL) has improved in recent years. This has partly been achieved by remission induction protocols incorporating high-dose methotrexate (HD-MTX) and rituximab. Given the high rates of relapse, consolidation therapy is usually considered in first response. Whole brain radiotherapy may prolong PFS but appears to confer no long-term survival advantage and is associated with significant neurocognitive dysfunction. Attempts to improve efficacy and reduce neurotoxicity of consolidation therapy have included thiotepa-based high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT)...
June 5, 2017: Bone Marrow Transplantation
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