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T-cells, bone marrow transplant

N Ben Abdejlil, D Belloumi, M Mâammar, R El Fatimi, L Torjman, A Lakhal, F Jenhani, S Hmida, T Ben Othman, S Ladeb
This study compared retrospectively the effectiveness, toxicity and hematopoietic recovery after autologous peripheral blood stem cell transplantation (ASCT) of two consecutive peripheral blood stem cell mobilization regimens in newly diagnosed MM patients. Patients in group 1 (n=178) were treated with 4 g/m(2) of cyclophosphamide (CY) plus G-CSF (5 μg/kg/day). Patients in group 2 (n=117) with 750 mg/m(2) of VP16 plus G-CSF (10 μg/kg/day). Optimal mobilization, defined by a target number of 8 × 10(6) CD34+ cells/kg collected, was achieved in 62...
October 24, 2016: Bone Marrow Transplantation
Yandong Zhang, Xinchun Yu, Shuhui Sun, Qian Li, Yunli Xie, Qiang Li, Yifan Zhao, Jianfeng Pei, Wenmin Zhang, Peng Xue, Zhijun Zhou, Yubin Zhang
The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells...
October 19, 2016: Toxicology and Applied Pharmacology
Xiaodan Luo, Lihua Xu, Yangqiu Li, Huo Tan
Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival...
October 21, 2016: Cell Biology and Toxicology
Shane Sinclair, Reanne Booker, Tak Fung, Shelley Raffin-Bouchal, Bert Enns, Kate Beamer, Naree Ager
PURPOSE/OBJECTIVES: To examine the relationships between spiritual, religious, and sociodemographic factors and post-traumatic growth, quality of life, and spiritual well-being in outpatients undergoing bone marrow and/or stem cell transplantation (BMSCT).
. DESIGN: Cross-sectional, descriptive, exploratory.
. SETTING: Outpatient bone marrow transplantation clinic at the Tom Baker Cancer Centre in Calgary, Alberta, Canada.
. SAMPLE: 100 patients (21 pre-BMSCT and 79 post-BMSCT) accrued consecutively via non-probability sampling...
November 1, 2016: Oncology Nursing Forum
Annalisa Ruggeri, Yuqian Sun, Myriam Labopin, Andrea Bacigalupo, Francesca Lorentino, William Arcese, Stella Santarone, Zafar Gülbas, Didier Blaise, Giuseppe Messina, Ardeshi Ghavamzadeh, Florent Malard, Benedetto Bruno, Jose Luis Diez-Martin, Yener Koc, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Severe graft-versus-host-disease is a major barrier for non T-cell-depleted haploidentical stem cell transplantation and there is no consensus on the optimal GVHD prophylaxis. This study compared the two most commonly used graft-versus-host-disease prophylaxis regimens (post-transplant-cyclophosphamide-based (PTCY) versus the anti-thymocyte-globulin-based (ATG)) in adults with acute myeloid leukemia reported to the european society for blood and bone marrow transplantation. 308 patients were analyzed, 193 received PTCY and 115 ATG as anti- graft-versus-host-disease prophylaxis...
October 6, 2016: Haematologica
Ashley I Beyer, Marcus O Muench
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen and liver was evaluated by flow cytometry 12 weeks after transplant...
October 19, 2016: Stem Cells and Development
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
Yuen Ting Lam, Laura Lecce, Joanne T M Tan, Christina A Bursill, David J Handelsman, Martin K C Ng
Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of genomic androgen action mediated by androgen receptor (AR), a ligand-activated nuclear transcription factor, remains poorly understood. Using an AR knockout mouse strain that contains a transcriptionally inactive AR (AR(Δex3)KO), we examined the role of AR genomic function in modulating androgen-mediated augmentation of ischemia-induced neovascularization. Castrated wildtype (AR(WT)) and AR(Δex3)KO mice were implanted with dihydrotestosterone (DHT) or placebo pellets following hindlimb ischemia (HLI)...
October 18, 2016: Endocrinology
Yifeng Cai, Shoubao Ma, Yuejun Liu, Huanle Gong, Qiao Cheng, Bo Hu, Yan Wu, Xiao Yu, Chen Dong, Kai Sun, Depei Wu, Haiyan Liu
The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs...
October 17, 2016: Cellular & Molecular Immunology
Mark W Lowdell, Amy Thomas
Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres...
October 17, 2016: British Journal of Haematology
M-T Rubio, M Bouillié, N Bouazza, T Coman, H Trebeden-Nègre, A Gomez, F Suarez, D Sibon, A Brignier, E Paubelle, S Nguyen-Khoc, M Cavazzana, O Lantz, M Mohty, S Urien, O Hermine
Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34(+), NK, conventional T, regulatory T and invariant NKT (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4(-) iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4(-) iNKT expansion capacity was predictive in PBSC grafts...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Asako Tajima, Isha Pradhan, Xuehui Geng, Massimo Trucco, Yong Fan
One of the hallmarks of modern medicine is the development of therapeutics that can modulate immune responses, especially the adaptive arm of immunity, for disease intervention and prevention. While tremendous progress has been made in the past decades, manipulating the thymus, the primary lymphoid organ responsible for the development and education of T lymphocytes, remains a challenge. One of the major obstacles is the difficulty to reproduce its unique extracellular matrix (ECM) microenvironment that is essential for maintaining the function and survival of thymic epithelial cells (TECs), the predominant population of cells in the thymic stroma...
October 12, 2016: Methods in Molecular Biology
Carla Cunha, Catarina R Almeida, Maria Inês Almeida, Andreia M Silva, Maria Molinos, Sofia Lamas, Catarina L Pereira, Graciosa Q Teixeira, António T Monteiro, Susana G Santos, Raquel M Gonçalves, Mário A Barbosa
: : Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site...
October 11, 2016: Stem Cells Translational Medicine
Khadega A Abuelgasim, Saeed Alshieban, Nada A Almubayi, Ayman Alhejazi, Abdulrahman R Jazieh
We describe the case of a young man with therapy-naive chronic myeloid leukemia who did not initially have any peripheral blood or bone marrow excess blasts but presented with extramedullary myeloid blast crises involving the central nervous system and multiple lymph nodes. Conventional cytogenetic tests were positive for t(9;22)(q34:q11) as well as for trisomy 8, 14 and 21 and del(16q). The patient's peripheral blood and bone marrow were positive for the BCR-ABL oncogene when analyzed by fluorescence in situ hybridization and polymerase chain reaction...
May 2016: Case Reports in Oncology
Y Mori, K Ikeda, T Inomata, G Yoshimoto, N Fujii, H Ago, T Teshima
Jak1/2 inhibitor ruxolitinib is a promising agent for treating steroid-refractory GvHD after allogeneic hematopoietic stem cell transplantation (SCT) to produce quick and durable responses. However, optimal dose and tapering schedule of ruxolitinib remain to be determined. Discontinuation of ruxolitinib in myelofibrosis often induces 'withdrawal syndrome' characterized by acute relapse of the disease, but this issue is not well addressed in the treatment of GvHD. Four patients with GvHD (one acute and three chronic) after SCT for myelofibrosis were treated with ruxolitinib...
October 10, 2016: Bone Marrow Transplantation
Suelen Martins Perobelli, Ana Carolina Terra Mercadante, Rômulo Gonçalves Galvani, Triciana Gonçalves-Silva, Ana Paula Gregório Alves, Antonio Pereira-Neves, Marlene Benchimol, Alberto Nóbrega, Adriana Bonomo
Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10(+) neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Laëtitia Le Texier, Katie E Lineburg, Benjamin Cao, Cameron McDonald-Hyman, Lucie Leveque-El Mouttie, Jemma Nicholls, Michelle Melino, Blessy C Nalkurthi, Kylie A Alexander, Bianca Teal, Stephen J Blake, Fernando Souza-Fonseca-Guimaraes, Christian R Engwerda, Rachel D Kuns, Steven W Lane, Michele Teng, Charis Teh, Daniel Gray, Andrew D Clouston, Susan K Nilsson, Bruce R Blazar, Geoffrey R Hill, Kelli P A MacDonald
Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival...
September 22, 2016: JCI Insight
Raffaella Greco, Lara Crucitti, Maddalena Noviello, Sara Racca, Daniele Mannina, Alessandra Forcina, Francesca Lorentino, Veronica Valtolina, Serena Rolla, Roee Dvir, Mara Morelli, Fabio Giglio, Maria Chiara Barbanti, Maria Teresa Lupo Stanghellini, Chiara Oltolini, Luca Vago, Paolo Scarpellini, Andrea Assanelli, Matteo G Carrabba, Sarah Marktel, Massimo Bernardi, Consuelo Corti, Massimo Clementi, Jacopo Peccatori, Chiara Bonini, Fabio Ciceri
Human herpesvirus 6 (HHV-6) is increasingly recognized as a potentially life-threatening pathogen in allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively evaluated 54 adult patients who developed positivity to HHV-6 after alloSCT. The median time from alloSCT to HHV-6 reactivation was 34 days. HHV-6 was present in plasma samples from 31 patients, in bone marrow (BM) of 9 patients, in bronchoalveolar lavage fluid and liver or gut biopsy specimens from 33 patients, and in cerebrospinal fluid of 7 patients...
September 30, 2016: Biology of Blood and Marrow Transplantation
Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells...
2016: Frontiers in Immunology
Dasaradha Jalapothu, Margherita Boieri, Rachel E Crossland, Pranali Shah, Isha A Butt, Jean Norden, Ralf Dressel, Anne M Dickinson, Marit Inngjerdingen
MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease...
2016: Frontiers in Immunology
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