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T-cells, hematopoietic cell transplant

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https://www.readbyqxmd.com/read/29445008/blockade-of-host-%C3%AE-2-adrenergic-receptor-enhances-graft-versus-tumor-effect-through-modulating-apcs
#1
Hemn Mohammadpour, Rachel O'Neil, Jingxin Qiu, Philip L McCarthy, Elizabeth A Repasky, Xuefang Cao
Allogeneic hematopoietic cell transplantation is a potential curative therapy for hematologic malignancies. Host APCs are pivotal to the desired graft-versus-tumor (GVT) effect. Recent studies have shown that β2-adrenergic receptor (β2AR) signaling can have an important impact on immune cell function, including dendritic cells (DCs). In this article, we demonstrate that pretreatment of host mice with a β2AR blocker significantly increases the GVT effect of donor CD8 + T cells by decreasing tumor burden without increasing graft-versus-host disease...
February 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#2
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29443409/cellular-collection-by-apheresis
#3
REVIEW
Anand Padmanabhan
Cellular collection is an important and increasingly used apheresis procedure. These collections are performed by leukocytapheresis, a procedure involving the removal of a patient's or donor's white blood cells, and are used to collect hematopoietic progenitor cells, specific cell populations (such as T-lymphocytes), and granulocytes. Hematopoietic progenitor cell apheresis and T-lymphocyte collection are performed by procedures that enrich for mononuclear cells. Hematopoietic progenitor cells are used for autologous and allogeneic hematopoietic stem cell transplantation, whereas T-cell collection is being used increasingly in novel cellular therapy approaches and for donor lymphocyte infusions to induce graft-versus-leukemia effect...
February 2018: Transfusion
https://www.readbyqxmd.com/read/29442161/allogeneic-hematopoietic-stem-cell-transplantation-in-primary-cutaneous-t-cell-lymphoma
#4
Laura Cudillo, Raffaella Cerretti, Alessandra Picardi, Benedetta Mariotti, Gottardo De Angelis, Maria Cantonetti, Massimiliano Postorino, Eleonora Ceresoli, Giovanna De Santis, Daniela Nasso, Francesco Pisani, Enrico Scala, Fabio Di Piazza, Alessandro Lanti
In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10...
February 13, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29438096/fda-approval-summary-lenalidomide-as-maintenance-therapy-after-autologous-stem-cell-transplant-in-newly-diagnosed-multiple-myeloma
#5
Elizabeth Dianne Pulte, Andrew Dmytrijuk, Lei Nie, Kirsten B Goldberg, Amy E McKee, Ann T Farrell, Richard Pazdur
On February 22, 2017, the U.S. Food and Drug Administration (FDA) granted approval for the use of lenalidomide as maintenance therapy after autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with multiple myeloma. The approval was based on evidence from two randomized, blinded trials of maintenance lenalidomide versus placebo in patients with myeloma who had undergone auto-HSCT along with a third trial of lenalidomide versus no therapy. Each of the trials demonstrated superior progression-free survival for the patients treated with lenalidomide...
February 7, 2018: Oncologist
https://www.readbyqxmd.com/read/29437593/%C3%AE-1-antitrypsin-infusion-for-treatment-of-steroid-resistant-acute-graft-versus-host-disease
#6
John M Magenau, Steven C Goldstein, Dan Peltier, Robert J Soiffer, Thomas Braun, Attaphol Pawarode, Mary M Riwes, Maggi Kennel, Joseph H Antin, Corey S Cutler, Vincent T Ho, Edwin P Alyea, Brian L Parkin, Gregory A Yanik, Sung Won Choi, Eli C Lewis, Charles A Dinarello, John Koreth, Pavan Reddy
Corticosteroid resistance following acute GVHD (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness due to poor response or excessive toxicity, primarily from infection. Alpha-1 antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by down-modulation of inflammation and increasing ratios of regulatory to effector T cells...
February 2, 2018: Blood
https://www.readbyqxmd.com/read/29431743/sorafenib-promotes-graft-versus-leukemia-activity-in-mice-and-humans-through-il-15-production-in-flt3-itd-mutant-leukemia-cells
#7
Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis Dong Hwan Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Sha, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar, Robert Zeiser
Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29431621/haploidentical-hsct-for-hemoglobinopathies-improved-outcomes-with-tcr%C3%AE-%C3%AE-cd19-depleted-grafts
#8
Javid Gaziev, Antonella Isgrò, Pietro Sodani, Katia Paciaroni, Gioia De Angelis, Marco Marziali, Michela Ribersani, Cecilia Alfieri, Alessandro Lanti, Tiziana Galluccio, Gaspare Adorno, Marco Andreani
We examined outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) using T-cell receptor αβ + (TCRαβ + )/CD19 + -depleted grafts (TCR group, 14 patients) in children with hemoglobinopathies. Patients received a preparative regimen consisting of busulfan, thiotepa, cyclophosphamide, and antithymocyte globulin preceded by fludarabine, hydroxyurea, and azathioprine. The median follow-up among surviving patients was 3.9 years. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 84% and 69%, respectively...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29427418/high-mutation-frequency-of-the-piga-gene-in-t-cells-results-in-reconstitution-of-gpi-anchor-cd52-t-cells-that-can-give-early-immune-protection-after-alemtuzumab-based-t-cell-depleted-allogeneic-stem-cell-transplantation
#9
Floris C Loeff, J H Frederik Falkenburg, Lois Hageman, Wesley Huisman, Sabrina A J Veld, H M Esther van Egmond, Marian van de Meent, Peter A von dem Borne, Hendrik Veelken, Constantijn J M Halkes, Inge Jedema
Alemtuzumab (ALM) is used for T cell depletion in the context of allogeneic hematopoietic stem cell transplantation (alloSCT) to prevent acute graft-versus-host disease and graft rejection. Following ALM-based T cell-depleted alloSCT, relatively rapid recovery of circulating T cells has been described, including T cells that lack membrane expression of the GPI-anchored ALM target Ag CD52. We show, in a cohort of 89 human recipients of an ALM-based T cell-depleted alloSCT graft, that early lymphocyte reconstitution always coincided with the presence of large populations of T cells lacking CD52 membrane expression...
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29426829/impaired-thymopoiesis-predicts-for-a-high-risk-of-severe-infections-after-reduced-intensity-conditioning-without-anti-thymocyte-globulin-in-double-umbilical-cord-blood-transplantation
#10
Lucia E Duinhouwer, Nick Beije, Bronno van der Holt, Anita Rijken-Schelen, Cor H Lamers, Judith Somers, Eric Braakman, Jan J Cornelissen
Umbilical cord blood stem cell transplantation (UCBT) is associated with retarded hematopoietic recovery and immune reconstitution and a high infection-related morbidity and mortality, especially after conditioning including anti-thymocyte globulin (ATG). However, data on immune recovery, incidence of infections, and outcome in double UCBT (dUCBT) recipients receiving an ATG-free reduced intensity conditioning (RIC) are lacking. In this study, recovery of lymphocyte subsets, thymopoiesis, and its association with severe infections and clinical outcome was assessed in a group of 55 recipients of a dUCBT ATG-free RIC regimen...
February 9, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29425515/reprint-of-virus-specific-t-cells-broadening-applicability
#11
REVIEW
A John Barrett, Susan Prockop, Catherine M Bollard
Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease...
March 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29423555/second-malignancies-after-hematopoietic-stem-cell-transplantation
#12
REVIEW
Ivetta Danylesko, Avichai Shimoni
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5-10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers...
February 8, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29416707/protein-dysregulation-in-graft-versus-host-disease
#13
REVIEW
Liren Qian, Delia Dima, Cristian Berce, Yu Liu, Ioana Rus, Lajos-Zsolt Raduly, Yi Liu, Bobe Petrushev, Ioana Berindan-Neagoe, Alexandru Irimie, Alina Tanase, Ancuta Jurj, Jianliang Shen, Ciprian Tomuleasa
Allogeneic hematopoietic stem cell transplantation is a well-established treatment for many malignant and non-malignant hematological disorders. As a frequent complication in up to 50% of all patients, graft-versus-host disease is still the main cause for morbidity and non-relapse mortality. Diagnosis is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally-recognized consensus has yet been established...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416633/allogeneic-hematopoietic-stem-cell-transplantation-for-relapsed-acute-myeloid-leukemia-in-eto-positive-with-reduced-intensity-conditioning
#14
Zhi Guo, Chen Xu, Hu Chen
Objective: This research is conducted under the intention of exploring the efficacy and safety of reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed ETO positive acute myeloid leukemia (AML). Materials and Methods: Treatment of 15 cases referring to recurrent ETO positive acute myeloid leukemia in an army hospital from January 2010 to January 2013 through allo-HSCT with reduced-intensity conditioning...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29410547/thyroid-dysfunction-in-adult-hematopoietic-cell-transplant-survivors-risks-and-outcomes
#15
Nosha Farhadfar, Marius N Stan, Pankaj Shah, Vikram Sonawane, Mehrdad T Hefazi, Hemant S Murthy, Fay Zou, Xiong Sican, Shahrukh K Hashmi
The incidence and risk factors for thyroid disorders among adult survivors of allogeneic hematopoietic stem cell transplantation (alloHCT) is not well known. This study evaluated incidence and risk factors of thyroid dysfunction in 259 adult alloHCT recipients who had survived for 2 years or more after transplant. Median follow-up was 4.6 years (range; 2.3 to 15.4 years). The 5-year cumulative incidence of thyroid dysfunction was 30.5% (79 of 259 patients). Majority of thyroid abnormalities were observed beyond 2 years after alloHCT...
February 6, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29410546/hla-mismatches-that-are-identical-for-the-antigen-recognition-domain-are-less-immunogenic
#16
Dave Roelen, Yvonne de Vaal, Cynthia Vierra-Green, Stephanie Waldvogel, Stephen Spellman, Frans Claas, Machteld Oudshoorn
For hematopoietic stem cell transplantation (HCT) HLA 10/10 (HLA-A, B, C, DRB1, DQB1) matched donors are optimal, but are not available for all patients. The identification of permissive/non-immunogenic mismatches may improve the outcome of HLA mismatched transplants. We hypothesize that HLA alleles identical within the antigen recognition domain (ARD), but mismatched outside the peptide binding groove or α-helices are often permissive mismatches. We evaluated the functional impact of non-ARD mismatches by performing in vitro functional T cell assays...
February 6, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29409743/tolerance-induction-in-hla-disparate-living-donor-kidney-transplantation-by-facilitating-cell-enriched-donor-stem-cell-infusion-the-importance-of-durable-chimerism
#17
REVIEW
Joseph R Leventhal, Suzanne T Ildstad
Successful solid organ transplantation currently requires the life-long use of medications to suppress the immune system in order to prevent transplant rejection. Drug-based immunosuppression significantly increases the risk of infection and cancer, as well as being very costly. Development of new therapies to minimize or eliminate entirely the need for anti-rejection drugs is of great interest to the transplant community. Therapeutic cell transfer for the control of the human immune system represents a compelling approach to reduce or eliminate the need for anti-rejection drugs...
February 2, 2018: Human Immunology
https://www.readbyqxmd.com/read/29408689/updated-follow-up-of-a-tolerance-protocol-in-hla-identical-renal-transplant-pairs-given-donor-hematopoietic-stem-cells
#18
REVIEW
Joseph R Leventhal, Joshua Miller, James M Mathew, Sunil Kurian, Anat R Tambur, John Friedewald, Jane Charrette, Michael M Abecassis
Kidney transplant recipients given donor hematopoietic stem cells from their HLA-identical living related donors have now been followed between 5 and 9 ½ years post-operatively. Recipients who were designated as tolerant (Tol) have remained so since the last report when the 5 year (biopsy associated) milestone was reached. There has been 1 mortality of a Tol patient, unrelated to the study protocol, while 5 (of 15) have remained Tol between 7 & 8 ½ years post-operatively. There has been continuing elevated T-regulatory (CD4+CD25HighCD127-FOXP3+) cells in PBMC previously reported on...
January 30, 2018: Human Immunology
https://www.readbyqxmd.com/read/29408506/higher-donor-apheresis-blood-volumes-are-associated-with-a-reduction-in-relapse-risk-and-improved-survival-in-reduced-intensity-allogeneic-transplants-with-unrelated-donors
#19
Lisa M Crisalli, Joanne T Hinkle, Christopher C Walling, Mary Sell, Noelle V Frey, Elizabeth O Hexner, Alison W Loren, Selina M Luger, Edward A Stadtmauer, David L Porter, Ran Reshef
Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) offers a curative option for patients with hematologic malignancies who are unable to undergo myeloablative conditioning, but its success is limited by high rates of relapse. Several studies have suggested a role for T-cell doses in peripheral blood stem-cell grafts in RIC HSCT. Since T-cell dose is typically not known until after the collection, and apheresis blood volume is easily modifiable, we hypothesized that higher donor apheresis blood volumes would improve transplant outcomes through an effect on graft composition...
February 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29407180/allogeneic-hematopoietic-cell-transplantation-in-t-cell-prolymphocytic-leukemia-a-single-center-experience
#20
Bhagirathbhai R Dholaria, Ernesto Ayala, Lubomir Sokol, Taiga Nishihori, Julio C Chavez, Mohammad Hussaini, Ambuj Kumar, Mohamed A Kharfan-Dabaja
BACKGROUND: T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited. PATIENTS AND METHODS: We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43-71) years who underwent allo-HCT for T-PLL...
January 29, 2018: Leukemia Research
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