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https://www.readbyqxmd.com/read/28092353/non-myeloablative-conditioning-for-second-hematopoietic-cell-transplantation-for-graft-failure-in-patients-with-non-malignant-disorders-a-prospective-study-and-review-of-the-literature
#1
K Mallhi, P J Orchard, W P Miller, Q Cao, J Tolar, T C Lund
Allogeneic hematopoietic cell transplantation (HCT) effectively treats several non-malignant disorders such as selected lysosomal disorders, cerebral adrenoleukodystrophy and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with non-malignant disorders who underwent a second allogenic HCT for GF using a non-myeloablative, low-dose busulfan-based regimen...
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28092350/long-term-renal-survival-in-patients-undergoing-t-cell-depleted-versus-conventional-hematopoietic-stem-cell-transplants
#2
I G Glezerman, S Devlin, M Maloy, M Bui, E A Jaimes, S A Giralt, A A Jakubowski
Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) for ⩾100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0...
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28092349/recipient-donor-hla-and-cmv-matching-in-recipients-of-t-cell-depleted-unrelated-donor-haematopoietic-cell-transplants
#3
B E Shaw, N P Mayor, R M Szydlo, W P Bultitude, C Anthias, K Kirkland, J Perry, A Clark, S Mackinnon, D I Marks, A Pagliuca, M N Potter, N H Russell, K Thomson, J A Madrigal, S G E Marsh
Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1...
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28091601/massively-parallel-digital-transcriptional-profiling-of-single-cells
#4
Grace X Y Zheng, Jessica M Terry, Phillip Belgrader, Paul Ryvkin, Zachary W Bent, Ryan Wilson, Solongo B Ziraldo, Tobias D Wheeler, Geoff P McDermott, Junjie Zhu, Mark T Gregory, Joe Shuga, Luz Montesclaros, Jason G Underwood, Donald A Masquelier, Stefanie Y Nishimura, Michael Schnall-Levin, Paul W Wyatt, Christopher M Hindson, Rajiv Bharadwaj, Alexander Wong, Kevin D Ness, Lan W Beppu, H Joachim Deeg, Christopher McFarland, Keith R Loeb, William J Valente, Nolan G Ericson, Emily A Stevens, Jerald P Radich, Tarjei S Mikkelsen, Benjamin J Hindson, Jason H Bielas
Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3' mRNA counting of tens of thousands of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6 min, with ∼50% cell capture efficiency. To demonstrate the system's technical performance, we collected transcriptome data from ∼250k single cells across 29 samples. We validated the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28070238/hematological-disorders-and-pulmonary-hypertension
#5
REVIEW
Rajamma Mathew, Jing Huang, Joseph M Wu, John T Fallon, Michael H Gewitz
Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death...
December 26, 2016: World Journal of Cardiology
https://www.readbyqxmd.com/read/28069109/immunomodulatory-effects-of-bone-marrow-mesenchymal-stem-cells-overexpressing-heme-oxygenase-1-protective-effects-on-acute-rejection-following-reduced-size-liver-transplantation-in-a-rat-model
#6
Zhong-Yang Shen, Bin Wu, Tao Liu, Yang Yang, Ming-Li Yin, Wei-Ping Zheng, Bo-Ya Zhang, Hong-Li Song
Here we explore the T-lymphocyte suppressive and immunomodulatory effects of bone marrow mesenchymal stem cells (BMMSCs) overexpressing heme oxygenase-1 (HO-1) on acute rejection following reduced-size liver transplantation (RLT) in a rat model. The proliferation activity, cell cycle progression, secretion of proinflammatory cytokines, expression of CD25 and CD71 in lymphocytes, and activity of NK cells were found to be significantly lowered, and the proportion of regulatory T cells (Tregs) was found to be increased relative to BMMSCs when Adv-HO-1/BMMSCs were co-cultured with Con A ex vivo; secretion of anti-inflammatory cytokines was significantly higher...
December 26, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28068330/loss-of-p53-induces-leukemic-transformation-in-a-murine-model-of-jak2-v617f-driven-polycythemia-vera
#7
T Tsuruta-Kishino, J Koya, K Kataoka, K Narukawa, Y Sumitomo, H Kobayashi, T Sato, M Kurokawa
As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of Jak2 V617F mutant into wild-type p53 murine bone marrow cells induced polycythemia vera (PV) in the recipient mice, whereas Jak2 V617F-transduced p53-null mice developed lethal leukemia after the preceding PV phase...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28067886/dose-adapted-post-transplant-cyclophosphamide-for-hla-haploidentical-transplantation-in-fanconi-anemia
#8
M S Thakar, C Bonfim, M C Walters, R Storb, R Pasquini, L Burroughs, B M Sandmaier, A Woolfrey, H-P Kiem
We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28067876/impact-of-wilms-tumor-1-expression-on-outcome-of-patients-undergoing-allogeneic-stem-cell-transplantation-for-aml
#9
R Duléry, O Nibourel, J Gauthier, V Elsermans, H Behal, V Coiteux, L Magro, A Renneville, A Marceau, T Boyer, B Quesnel, C Preudhomme, A Duhamel, I Yakoub-Agha
The monitoring of the minimal residual disease by Wilms' tumor 1 expression (MRD(WT1)) is a standardized test, which can be used in over 80% of patients with AML. To investigate the prognostic value of MRD(WT1) in patients undergoing allogeneic stem cell transplantation (allo-SCT) for AML, MRD(WT1) was monitored 3 months after transplantation in 139 patients. MRD(WT1) positivity did not lead to any therapeutic intervention. Median follow-up was 39.3 (6.4-99.8) months. Patients with positive MRD(WT1) at 3 months experienced more often post-transplant relapse (27/30, 90%) than those with negative MRD(WT1) (16/109, 14...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28067872/reduced-intensity-and-non-myeloablative-allogeneic-stem-cell-transplantation-from-alternative-hla-mismatched-donors-for-hodgkin-lymphoma-a-study-by-the-french-society-of-bone-marrow-transplantation-and-cellular-therapy
#10
J Gauthier, L Castagna, F Garnier, T Guillaume, G Socié, S Maury, N Maillard, R Tabrizi, T Marchand, J Malfuson, A Gac, E Gyan, M Mercier, Y Béguin, J Delage, P Turlure, A Marçais, S Nguyen, R Dulery, J Bay, A Huynh, E Daguindau, J Cornillon, C Régny, M Michallet, R Peffault de Latour, I Yakoub-Agha, D Blaise
Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28066800/cd36-deficiency-impairs-the-small-intestinal-barrier-and-induces-subclinical-inflammation-in-mice
#11
Vincenza Cifarelli, Stoyan Ivanov, Yan Xie, Ni-Huiping Son, Brian T Saunders, Terri A Pietka, Trevor M Shew, Jun Yoshino, Sinju Sundaresan, Nicholas O Davidson, Ira J Goldberg, Andrew E Gelman, Bernd H Zinselmeyer, Gwendalyn J Randolph, Nada A Abumrad
BACKGROUND & AIMS: CD36 has immuno-metabolic actions and is abundant in the small intestine on epithelial, endothelial and immune cells. We examined the role of CD36 in gut homeostasis using mice null for CD36 (CD36KO) and with CD36 deletion specific to enterocytes (Ent-CD36KO) or endothelial cells (EC-CD36KO). METHODS: Intestinal morphology was evaluated using immunohistochemistry and electron microscopy (EM). Intestinal inflammation was determined from neutrophil infiltration and expression of cytokines, toll-like receptors and COX-2...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28064242/cyclin-dependent-kinase-5-activity-is-required-for-allogeneic-t-cell-responses-after-hematopoietic-cell-transplantation-in-mice
#12
David Askew, Tej Pareek, Saada Eid, Sudipto Ganguly, Megan Tyler, Alex Y Huang, John J Letterio, Kenneth R Cooke
Molecular intermediates in T cell activation pathways are crucial targets for the therapy and prevention of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT). We recently identified an essential role for cyclin dependent kinase 5 (Cdk5) in T cell activation and effector function, but the contribution of Cdk5 activity to the development of GVHD has not been explored. Using an established, pre-clinical, murine, GVHD model we reveal that Cdk5 activity is increased in key target organs early after allogeneic HCT...
November 14, 2016: Blood
https://www.readbyqxmd.com/read/28056320/-clinical-analysis-in-a-cohort-of-102-patients-with-myelodysplastic-syndrome-characterized-by-erythroid-hyperplasia
#13
Y Yu, A N Sun, S N Chen, Q R Wang, T T Zhang, D P Wu
Objective: To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome (MDS) and erythroid hyperplasia. Methods: MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study. The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia(MDS-E). The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University...
January 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28056234/-effect-of-intracoronary-autologous-bone-marrow-mononuclear-cells-transplantation-on-arrhythmia-in-canines
#14
J Tang, G Y Sun, T Chen, Y D Wang, J Zhang, X Q Qi
Objective: To observe the survival and the differentiation of grafted bone marrow cells (BM-MNCs) in host myocardium. To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins, important mediator for arrhythmia genesis after myocardial infarction. Methods: Acute myocardial infarction (AMI) was induced by left anterior descending coronary artery (LAD) ligation in hybrid canine. BM-MNCs suspension was prepared by density centrifugation...
December 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28049637/low-immunosuppressive-burden-after-hla-matched-related-or-unrelated-bmt-using-post-transplantation-cyclophosphamide
#15
Christopher G Kanakry, Javier Bolaños-Meade, Yvette L Kasamon, Marianna Zahurak, Nadira Durakovic, Terry Furlong, Marco Mielcarek, Marta Medeot, Ivana Gojo, B Douglas Smith, Jennifer A Kanakry, Ivan M Borrello, Robert A Brodsky, Douglas E Gladstone, Carol Ann Huff, William H Matsui, Lode J Swinnen, Kenneth R Cooke, Richard F Ambinder, Ephraim J Fuchs, Marcos J de Lima, Borje S Andersson, Ravi Varadhan, Paul V O'Donnell, Richard J Jones, Leo Luznik
The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Post-transplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched-related (MRD) or HLA-matched-unrelated (MUD) T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28039267/potent-anti-leukemia-activities-of-chimeric-antigen-receptor-modified-t-cells-against-cd19-in-chinese-patients-with-relapsed-refractory-acute-lymphocytic-leukemia
#16
Yongxian Hu, Zhao Wu, Yi Luo, Jimin Shi, Jian Yu, Chengfei Pu, Zhuyu Liang, Guoqing Wei, Qu Cui, Jie Sun, Jing Jiang, Jue Xie, Yamin Tan, Wanmao Ni, Jifang Tu, Jinping Wang, Aiyun Jin, Hao Zhang, Zhen Cai, Lei Xiao, He Huang
PURPOSE: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor modified T cells against CD19 (CART19s) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. STUDY DESIGN: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine- and cyclophosphamide-based lymphodepletion. The post-infusion responses, toxicities, expansion and persistence of CART19s in enrolled patients were observed and monitored...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28039266/malignant-astrocytic-tumor-progression-potentiated-by-jak-mediated-recruitment-of-myeloid-cells
#17
Prajwal Rajappa, William S Cobb, Emma Vartanian, Yujie Huang, Laura Daly, Caitlin Hoffman, Jane Zhang, Beiyi Shen, Rachel Yanowitch, Kunal Garg, Babacar Cisse, Sara Haddock, Jason T Huse, David J Pisapia, Timothy A Chan, David Lyden, Jacqueline Bromberg, Jeffrey P Greenfield
PURPOSE: While the tumor microenvironment has been known to play an integral role in tumor progression, the function of non-resident bone marrow-derived cells (BMDCs) remains to be determined in neurological tumors. Here we identified the contribution of BMDC recruitment in mediating malignant transformation from low- to high-grade gliomas. EXPERIMENTAL DESIGN: We analyzed human blood and tumor samples from patients with low- and high-grade gliomas. A spontaneous platelet derived growth factor (PDGF) murine glioma model (RCAS) was utilized to recapitulate human disease progression...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28039079/post-transplant-cyclophosphamide-and-tacrolimus-mycophenolate-mofetil-combination-prevents-graft-versus-host-disease-in-allogeneic-peripheral-blood-hematopoietic-cell-transplantation-from-hla-identical-donors
#18
Fabrizio Carnevale-Schianca, Daniela Caravelli, Susanna Gallo, Valentina Coha, Lorenzo D'Ambrosio, Elena Vassallo, Marco Fizzotti, Francesca Nesi, Luisa Gioeni, Massimo Berger, Alessandra Polo, Loretta Gammaitoni, Paolo Becco, Lidia Giraudo, Monica Mangioni, Dario Sangiolo, Giovanni Grignani, Delia Rota-Scalabrini, Antonino Sottile, Franca Fagioli, Massimo Aglietta
Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors...
December 27, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28035072/%C3%AE-np73-overexpression-promotes-resistance-to-apoptosis-but-does-not-cooperate-with-pml-rara-in-the-induction-of-an-apl-leukemic-phenotype
#19
Antonio R Lucena-Araujo, Juan L Coelho-Silva, Diego A Pereira-Martins, Carolina Thomé, Priscila S Scheucher, Ana P Lange, Helder H Paiva, Benjamin T Hemmelgarn, Mariana C Morais-Sobral, Elisa A Azevedo, Pedro L Franca-Neto, Rafael F Franca, Cleide L Silva, Alexandre Krause, Eduardo M Rego
Here, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025979/driving-gene-engineered-t-cell-immunotherapy-of-cancer
#20
REVIEW
Laura A Johnson, Carl H June
Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy...
January 2017: Cell Research
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