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T-cells, hematopoietic cell transplant

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https://www.readbyqxmd.com/read/29224778/rapid-mobilization-reveals-a-highly-engraftable-hematopoietic-stem-cell
#1
Jonathan Hoggatt, Pratibha Singh, Tiffany A Tate, Bin-Kuan Chou, Shruti R Datari, Seiji Fukuda, Liqiong Liu, Peter V Kharchenko, Amir Schajnovitz, Ninib Baryawno, Francois E Mercier, Joseph Boyer, Jason Gardner, Dwight M Morrow, David T Scadden, Louis M Pelus
Hematopoietic stem cell transplantation is a potential curative therapy for malignant and nonmalignant diseases. Improving the efficiency of stem cell collection and the quality of the cells acquired can broaden the donor pool and improve patient outcomes. We developed a rapid stem cell mobilization regimen utilizing a unique CXCR2 agonist, GROβ, and the CXCR4 antagonist AMD3100. A single injection of both agents resulted in stem cell mobilization peaking within 15 min that was equivalent in magnitude to a standard multi-day regimen of granulocyte colony-stimulating factor (G-CSF)...
November 17, 2017: Cell
https://www.readbyqxmd.com/read/29224314/-clinical-value-of-pcr-for-viral-detection-of-bronchoalveolar-lavage-fluid-in-the-diagnosis-and-treatment-of-pneumonia-after-allogeneic-hematopoietic-stem-cell-transplantation
#2
Y Y Chen, X Y Luo, X S Zhao, Z H Jiang, Y Chen, H Chen, X D Mo, W Han, F R Wang, J Z Wang, C H Yan, Y Q Sun, Y Y Zhang, T T Han, F F Tang, H X Fu, S Zhang, Y Wang, L P Xu, X H Zhang, K Y Liu, X J Huang
Objective: To analyze the clinical value of real-time PCR for virus detection in the diagnosis and treatment of patients after allo-HSCT who had no infection evidence of pneumonia using routine pathogen detection panel. Methods: The clinical data of 71 episodes with acute lung injury from May 2015 to March 2017 after allo-HSCT in hematology department of Peking University People's Hospital (PKUPH) were retrospectively analyzed. PCR for virus detection and other routine pathogen detection tests were performed on bronchoalveolar lavage fluid (BALF) samples...
November 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29223388/transplantation-in-the-treatment-of-primary-cutaneous-aggressive-epidermotropic-cytotoxic-cd8-positive-t-cell-lymphoma
#3
Benoit M Cyrenne, Juliet Fraser Gibson, Antonio Subtil, Michael Girardi, Iris Isufi, Stuart Seropian, Francine Foss
BACKGROUND: Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T-cell lymphoma (CD8+ PCAETL) is a rare subtype of peripheral T-cell lymphoma with poor outcomes and without a standardized treatment strategy. Allogeneic hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy. PATIENTS AND METHODS: We conducted a retrospective case series. We identified 8 patients with the diagnosis of CD8+ PCAETL, 4 of whom also underwent allogeneic HSCT...
December 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29222325/cells-to-prevent-treat-relapse-following-allogeneic-stem-cell-transplantation
#4
REVIEW
Andrew C Dietz, Alan S Wayne
Relapse of cancer remains one of the primary causes of treatment failure and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A multitude of approaches have been used in the management of posttransplant relapse. This review focuses on recent data with cellular therapies designed to treat or prevent posttransplant relapse of hematologic malignancies, although many of these therapeutic approaches also have applications to solid tumors and in the nontransplant setting. Currently available cell therapies include second transplant, natural killer cells, monocyte-derived dendritic cell vaccines, and lymphocytes via donor lymphocyte infusion, antigen-primed cytotoxic T lymphocytes, cytokine-induced killer cells, marrow-infiltrating lymphocytes, and chimeric antigen receptor T cells...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#5
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222315/extracorporeal-photopheresis-cellular-therapy-for-the-treatment-of-acute-and-chronic-graft-versus-host-disease
#6
REVIEW
Jennifer Schneiderman
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used to prevent and treat acute and chronic graft-versus-host disease (a/cGVHD), they continue to negatively affect outcomes of HSCT significantly. Standard, first-line treatment consists of corticosteroids; beyond this, there is little consistency in therapeutic regimens. Current options include the addition of various immunosuppressive agents, the use of which puts patients at even higher risks for infection and other morbidities...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222242/treatment-of-inherited-bone-marrow-failure-syndromes-beyond-transplantation
#7
REVIEW
Rodrigo T Calado, Diego V Clé
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221143/impact-of-human-mesenchymal-stromal-cells-on-antifungal-host-response-against-aspergillus-fumigatus
#8
Stanislaw Schmidt, Lars Tramsen, Andreas Schneider, Ralf Schubert, Ada Balan, Özer Degistirici, Roland Meisel, Thomas Lehrnbecher
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215832/-activation-of-regeneration-of-red-and-white-pulp-of-the-spleen-after-the-combined-transplantation-of-hsc-and-mscs-in-terms-of-exposure-to-ionizing-radiation
#9
I Yu Maklakova, D Yu Grebnev, A P Yastrebov
The purpose of this work was to study the effect of combined transplantation of multipotent mesenchymal stromal (MSCS) and hematopoietic stem cells (HSCs) isolated from the placenta, on the regeneration of white and red pulp of the spleen under physiological conditions and in conditions of exposure to ionizing radiation. Methods. The experiments were performed with laboratory mice-males. We studied the influence of ionizing radiation dose of 4.0 Gy. Animals of the experimental group were intravenously infused into MMSC and GSK respectively at a dose of 6 million cells/kg and 330 thousand cells/kg, suspended in 0...
April 2017: Patologicheskaia Fiziologiia i èksperimental'naia Terapiia
https://www.readbyqxmd.com/read/29213274/natural-killer-cells-in-antifungal-immunity
#10
REVIEW
Stanislaw Schmidt, Lars Tramsen, Thomas Lehrnbecher
Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212909/pd-l1-prevents-the-development-of-autoimmune-heart-disease-in-graft-versus-host-disease
#11
Kathryn W Juchem, Faruk Sacirbegovic, Cuiling Zhang, Arlene H Sharpe, Kerry Russell, Jennifer M McNiff, Anthony J Demetris, Mark J Shlomchik, Warren D Shlomchik
Effector memory T cells (TEM) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (TN). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD because of increased sensitivity to PD-ligands...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29212046/hematopoietic-defects-in-response-to-reduced-arhgap21
#12
Juliana Xavier-Ferrucio, Lauremília Ricon, Karla Vieira, Ana Leda Longhini, Mariana Lazarini, Carolina Louzão Bigarella, Gilberto Franchi, Diane S Krause, Sara T O Saad
Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP) family, which function as negative regulators of Rho GTPases. Arhgap21 has been implicated in adhesion and migration of cancer cells. However, the role of Arhgap21 has never been investigated in hematopoietic cells. Herein, we evaluated functional aspects of hematopoietic stem and progenitor cells (HSPC) using a haploinsufficient (Arhgap21+/-) mouse. Our results show that Arhgap21+/- mice have an increased frequency of phenotypic HSC, impaired ability to form progenitor colonies in vitro and decreased hematopoietic engraftment in vivo, along with a decrease in LSK cell frequency during serial bone marrow transplantation...
November 23, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29209333/inhibition-of-acute-graft-versus-host-disease-with-retention-of-graft-versus-tumor-effects-by-dimethyl-fumarate
#13
Jingjing Han, Shoubao Ma, Huanle Gong, Shuangzhu Liu, Lei Lei, Bo Hu, Yang Xu, Haiyan Liu, Depei Wu
Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29208403/efficacy-of-standard-dose-r-chop-alternating-with-r-hdac-followed-by-autologous-hematopoietic-cell-transplantation-as-initial-therapy-of-mantle-cell-lymphoma-a%C3%A2-single-institution-experience
#14
Yazeed Sawalha, Brian T Hill, Lisa A Rybicki, Danyu Sun, Robert M Dean, Deepa Jagadeesh, Betty K Hamilton, Aaron T Gerds, Ronald M Sobecks, Steven Andresen, Hien K Liu, Navneet S Majhail, Brad Pohlman, Matt E Kalaycio, Brian J Bolwell, Mitchell R Smith
BACKGROUND: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone. PATIENTS AND METHODS: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC...
December 2, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29204910/who-is-the-patient-at-risk-of-cmv-recurrence-a-review-of-the-current-scientific-evidence-with-a-focus-on-hematopoietic-cell-transplantation
#15
REVIEW
Jan Styczynski
Cytomegalovirus (CMV) is an agent of global infection, and its acquisition in a population is characterized by an age-dependent rise in seropositivity. After primary infection, CMV remains in the host cells in latent form, and it can reactivate in the case of immune suppression. The risk of CMV recurrence is dependent on the level of incompetency of the immune system, manifested as an impairment of T-cell immunity, including the presence and function of CMV-specific cytotoxic T lymphocytes. This article presents data on the incidence of CMV recurrence in groups of immunocompromised patients, including allogeneic hematopoietic stem cell transplantation (HSCT) patients and other groups of patients, based on a summary of reported data...
December 4, 2017: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/29202481/bone-marrow-drives-central-nervous-system-regeneration-after-radiation-injury
#16
Jorg Dietrich, Ninib Baryawno, Naema Nayyar, Yannis K Valtis, Betty Yang, Ina Ly, Antoine Besnard, Nicolas Severe, Karin U Gustafsson, Ovidiu C Andronesi, Tracy T Batchelor, Amar Sahay, David T Scadden
Nervous system injury is a frequent result of cancer therapy involving cranial irradiation, leaving patients with marked memory and other neurobehavioral disabilities. Here, we report an unanticipated link between bone marrow and brain in the setting of radiation injury. Specifically, we demonstrate that bone marrow-derived monocytes and macrophages are essential for structural and functional repair mechanisms, including regeneration of cerebral white matter and improvement in neurocognitive function. Using a granulocyte-colony stimulating factor (G-CSF) receptor knockout mouse model in combination with bone marrow cell transplantation, MRI, and neurocognitive functional assessments, we demonstrate that bone marrow-derived G-CSF-responsive cells home to the injured brain and are critical for altering neural progenitor cells and brain repair...
December 4, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29200404/stat5bn642h-is-a-driver-mutation-for-t-cell-neoplasia
#17
Ha Thi Thanh Pham, Barbara Maurer, Michaela Prchal-Murphy, Reinhard Grausenburger, Eva Grundschober, Tahereh Javaheri, Harini Nivarthi, Auke Boersma, Thomas Kolbe, Mohamed Elabd, Florian Halbritter, Jan Pencik, Zahra Kazemi, Florian Grebien, Markus Hengstschläger, Lukas Kenner, Stefan Kubicek, Matthias Farlik, Christoph Bock, Peter Valent, Mathias Müller, Thomas Rülicke, Veronika Sexl, Richard Moriggl
STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that expressed either human STAT5B or STAT5BN642H in the hematopoietic compartment. While STAT5B-expressing mice lacked a hematopoietic phenotype, the STAT5BN642H-expressing mice rapidly developed T cell neoplasms. Neoplasia manifested as transplantable CD8+ lymphoma or leukemia, indicating that the STAT5BN642H mutation drives cancer development...
December 4, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29200163/therapy-related-acute-myeloid-leukemia-after-the-treatment-of-primary-solid-cancer-in-children-a-single-center-experience
#18
Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin
Therapy-related acute myeloid leukemia (t-AML) has a dismal prognosis and is one of the most frequent second malignant neoplasms which could be encountered by pediatric oncologists. Between October 2000 and September 2016, 16 patients who had primary solid tumors were diagnosed with t-AML at the Seoul National University Children's Hospital. The median patient age at the time of diagnosis of their primary solid tumors was 9.6 years (range, 0.1 to 15.4 y), and that of t-AML was 14.0 years (range, 4.7 to 23...
December 1, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29197681/t-cell-replete-haploidentical-transplantation-with-post-transplant-cyclophosphamide-for-hodgkin-lymphoma-relapsed-after-autologous-transplant-reduced-incidence-of-relapse-and-of-chronic-gvhd-compared-to-hla-identical-related-donors
#19
Jacopo Mariotti, Raynier Devillier, Stefania Bramanti, Barbara Sarina, Sabine Furst, Angela Granata, Catherine Faucher, Samia Harbi, Lucio Morabito, Christian Chabannon, Carmelo Carlo-Stella, Reda Bouabdallah, Armando Santoro, Didier Blaise, Luca Castagna
Allogeneic hematopoietic stem cell transplant (SCT) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) relapsing after autologous transplant (ASCT), but the incidence of disease relapse is still high. We performed a retrospective study on 64 patients with HL relapsing after ASCT in order to compare the outcome after HLA identical (HLAid-SCT, n=34) or haploidentical SCT with post-transplant cyclophosphamide (PT-Cy) (Haplo-SCT, n=30). All patients engrafted with a median time for neutrophil and platelet engraftment significantly shorter after HLAid compared with Haplo-SCT (14 vs 19 days and 11 vs 23 days, p<0...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29197675/japanese-recipients-who-receive-hla-matched-hematopoietic-cell-transplantation-for-their-myeloid-leukemia-have-an-advantage-to-prevent-recurrence-if-they-have-homozygous-hla-c1
#20
Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung-Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem-cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize human leukocyte antigen (HLA)-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and a frequent KIR2DL1 possession are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematological malignancies by assessing the data of 10,638 patients from the Japanese national registry...
November 29, 2017: Biology of Blood and Marrow Transplantation
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