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https://www.readbyqxmd.com/read/29035396/successful-correction-of-familial-hemophagocytic-lymphohistiocytosis-using-prenatal-genetic-testing-and-preemptive-hematopoietic-stem-cell-transplantation
#1
T F Michniacki, J M Mulcahy Levy, R R Quinones, R H Giller
No abstract text is available yet for this article.
October 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29032736/coccidioidomycosis-immunoglobulin-deficiency-safety-challenges-with-car-t-cells-therapy-for-relapsed-lymphoma
#2
Umar Zahid, Al-Aman Shaukat, Nida Hassan, Faiz Anwer
Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT...
October 2017: Immunotherapy
https://www.readbyqxmd.com/read/29032733/car-t-cells-and-allogeneic-hematopoietic-stem-cell-transplantation-for-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia
#3
Jun Liu, Xi Zhang, Jiang F Zhong, Cheng Zhang
Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL...
October 2017: Immunotherapy
https://www.readbyqxmd.com/read/29032276/reversal-of-low-donor-chimerism-following-hematopoietic-cell-transplantation-using-pentostatin-and-donor-lymphocyte-infusion-a-prospective-phase-ii-multicenter-trial
#4
Merav Bar, Mary E D Flowers, Barry E Storer, Thomas R Chauncey, Michael A Pulsipher, Monica S Thakar, Wolfgang Bethge, Rainer Storb, David G Maloney, Brenda M Sandmaier
In a multicenter prospective Phase II study, we evaluated the safety and efficacy of pentostatin followed by donor lymphocyte infusion (DLI) in patients with low donor T-cell chimerism after allogeneic hematopoietic cell transplantation (HCT). Thirty-six patients with low donor blood CD3 chimerism were enrolled in this study. Thirty-five patients received a total of 41 DLIs following a dose of pentostatin, and one patient received pentostatin only. Median donor CD3 chimerism prompting the initiation of pentostatin/DLI was 28 (5 to 47)%...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-human-leukocyte-antigen-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplant-for-chronic-lymphocytic-leukemia-cll
#5
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplant (allo-HCT) for medically fit patients. Although the use of allo-HCT has reduced since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT as it represents the only known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29032062/virus-specific-t-cells-broadening-applicability
#6
REVIEW
A John Barrett, Susan Prockop, Catherine M Bollard
Virus infection still remains an appreciable cause of morbidity and mortality after Hematopoietic stem cell transplant (HSCT). While pharmacotherapy and/or antibody therapy may help to 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 (e.g. Ad and BKV), 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-transplant without causing GvHD...
October 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29027124/tak1-inhibition-ameliorates-survival-from-graft-versus-host-disease-in-an-allogeneic-murine-marrow-transplantation-model
#7
Ayako Kobayashi, Shinichi Kobayashi, Kosuke Miyai, Yukiko Osawa, Toshikatsu Horiuchi, Shoichiro Kato, Takaaki Maekawa, Takeshi Yamamura, Junichi Watanabe, Ken Sato, Hitoshi Tsuda, Fumihiko Kimura
Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT). Majority of the current immunosuppressive strategies targeting donor T cells to prevent or treat acute GVHD are only partially effective, and often require escalated immunosuppressive therapy. Recent studies have revealed that activation of antigen-presenting cells in the proinflammatory milieu is important for the priming and promotion of GVHD. This activation is mediated by innate immune signaling pathways, which therefore potentially represent new targets in addressing GVHD...
October 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29025591/identification-of-a-novel-csf3r-sptan1-fusion-gene-in-an-atypical-chronic-myeloid-leukemia-patient-with-t-1-9-p34-q34-by-rna-seq
#8
Guangying Sheng, Jian Zhang, Zhao Zeng, Jinlan Pan, Qinrong Wang, Lijun Wen, Yang Xu, Depei Wu, Suning Chen
Membrane-proximal and truncated mutations of colony-stimulating factor 3 receptor (CSF3R) are frequently found in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). However, rearrangement involving CSF3R in hematological neoplasms has not been reported. Here, we report a case of a 21-year-old female diagnosed as aCML with t(1;9)(p34;q34) who presented a CSF3R rearrangement. First, RNA sequencing identified a novel fusion transcript involving exon 17 of CSF3R and exon 50 of non-erythrocytic-1-spectrin-alpha (SPTAN1)...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025287/-incidence-and-treatment-of-extranodal-natural-killer-t-cell-lymphoma-nasal-type-hungarian-experiences
#9
Annamária Bakos, Árpád Szomor, Tamás Schneider, Zsófia Miltényi, Imelda Marton, Zita Borbényi, Judit Pammer, László Krenács, Enikő Bagdi, Klára Piukovics
INTRODUCTION: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical behavior according to WHO 2016 classification. AIM: ENKTL has distinctive geographic distribution with higher incidence in Asia and Latin America (10% of all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline-based chemotherapy regimens are largely ineffective in the treatment of ENKTL...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29024803/graft-derived-reconstitution-of-mucosal-associated-invariant-t-cells-after-allogeneic-hematopoietic-cell-transplantation
#10
Abir Bhattacharyya, Laïla-Aïcha Hanafi, Alyssa Sheih, Jonathan L Golob, Sujatha Srinivasan, Michael J Boeckh, Steven A Pergam, Sajid Mahmood, Kelsey K Baker, Ted A Gooley, Filippo Milano, David N Fredricks, Stanley R Riddell, Cameron J Turtle
Mucosal-associated invariant T (MAIT) cells express a semi-invariant Vα7.2(+) T cell receptor (TCR) that recognizes ligands from distinct bacterial and fungal species. In neonates, MAIT cells proliferate coincident with gastrointestinal (GI) bacterial colonization. In contrast, under non-inflammatory conditions adult MAIT cells remain quiescent due to acquired regulation of TCR signaling. Effects of inflammation and the altered GI microbiota after allogeneic hematopoietic cell transplantation (HCT) on MAIT cell reconstitution have not been described...
October 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29023759/cord-blood-derived-t-cells-allow-the-generation-of-a-more-na%C3%A3-ve-tumor-reactive-cytotoxic-t-cell-phenotype
#11
Julian Kwoczek, Sebastian B Riese, Sabine Tischer, Szilvia Bak, Julia Lahrberg, Mathias Oelke, Holger Maul, Rainer Blasczyk, Martin Sauer, Britta Eiz-Vesper
BACKGROUND: Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord blood (CB) is well established. HSCs from CB are associated with a lower risk of graft-versus-host disease (GVHD), but antigen-independent expanded CB- and PB-derived T cells can induce GVHD in allo-HSC recipients. CB-derived cells might be more suitable for adoptive immunotherapy as they have unique T-cell characteristics. Here, we describe functional differences between CB and PB T cells stimulated with different cytokine combinations involved in central T-cell activation...
October 11, 2017: Transfusion
https://www.readbyqxmd.com/read/29023488/transgenic-expression-of-human-cytokines-in-immunodeficient-mice-does-not-facilitate-myeloid-expansion-of-bcr-abl1-transduced-human-cord-blood-cells
#12
Maria Askmyr, Sofia von Palffy, Nils Hansen, Niklas Landberg, Carl Högberg, Marianne Rissler, Helena Ågerstam, Thoas Fioretos
Several attempts have been made to model chronic myeloid leukemia (CML) in a xenograft setting but expansion of human myeloid cells in immunodeficient mice has proven difficult to achieve. Lack of cross-reacting cytokines in the microenvironment of the mice has been proposed as a potential reason. In this study we have used NOD/SCID IL2-receptor gamma deficient mice expressing human SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human, and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human cells in order to model CML...
2017: PloS One
https://www.readbyqxmd.com/read/29023267/enhanced-th17-responses-in-patients-with-il10-receptor-deficiency-and-infantile-onset-ibd
#13
Dror S Shouval, Liza Konnikova, Alexandra E Griffith, Sarah M Wall, Amlan Biswas, Lael Werner, Moran Nunberg, Jochen Kammermeier, Jeremy A Goettel, Rajsavi Anand, Hannah Chen, Batia Weiss, Jian Li, Anthony Loizides, Baruch Yerushalmi, Tadahiro Yanagi, Rita Beier, Laurie S Conklin, Christen L Ebens, Fernanda G M S Santos, Mary Sherlock, Jeffery D Goldsmith, Daniel Kotlarz, Sarah C Glover, Neil Shah, Athos Bousvaros, Holm H Uhlig, Aleixo M Muise, Christoph Klein, Scott B Snapper
BACKGROUND: IL10 receptor (IL10R) deficiency causes severe infantile-onset inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be important for innate and adaptive immune cell functions in mice. We have previously reported a key role of IL10 in the generation and function of human anti-inflammatory macrophages. Independent of innate immune cell defects, the aim of the current study was to determine the role of IL10R signaling in regulating human CD4 T-cell function...
October 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29021228/immune-reconstitution-and-survival-of-100-scid-patients-post-hematopoietic-cell-transplant-a-pidtc-natural-history-study
#14
Jennifer Heimall, Brent R Logan, Morton J Cowan, Luigi D Notarangelo, Linda M Griffith, Jennifer M Puck, Donald B Kohn, Michael A Pulsipher, Suhag Parikh, Caridad Martinez, Neena Kapoor, Richard O'Reilly, Michael Boyer, Sung-Yun Pai, Frederick Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica Thakar, James Connelly, Geoff Cuvelier, Blachy Davila, Evan Shereck, Alan Knutsen, Kathleen E Sullivan, Kenneth DeSantes, Alfred Gillio, Elie Haddad, Aleksandra Petrovic, Troy Quigg, Angela R Smith, Elizabeth Stenger, Ziyan Yin, William T Shearer, Thomas Fleisher, Rebecca H Buckley, Christopher C Dvorak
The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010-2014, including 68 with typical SCID and 32 with leaky SCID, Omenn Syndrome or Reticular Dysgenesis. Most (59%) were diagnosed by newborn screening or family history. The 2-year overall survival (OS) was 90%but was 95% for those infection-free at HCT vs...
October 11, 2017: Blood
https://www.readbyqxmd.com/read/29021165/preclinical-modeling-highlights-the-therapeutic-potential-of-hematopoietic-stem-cell-gene-editing-for-correction-of-scid-x1
#15
Giulia Schiroli, Samuele Ferrari, Anthony Conway, Aurelien Jacob, Valentina Capo, Luisa Albano, Tiziana Plati, Maria C Castiello, Francesca Sanvito, Andrew R Gennery, Chiara Bovolenta, Rahul Palchaudhuri, David T Scadden, Michael C Holmes, Anna Villa, Giovanni Sitia, Angelo Lombardo, Pietro Genovese, Luigi Naldini
Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of corrected cells and might affect the feasibility and safety of clinical translation. These concerns need to be addressed in stringent preclinical models and overcome by developing more efficient editing methods. We generated a humanized X-linked severe combined immunodeficiency (SCID-X1) mouse model and evaluated the efficacy and safety of hematopoietic reconstitution from limited input of functional HSPCs, establishing thresholds for full correction upon different types of conditioning...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29020348/kinetics-of-double-stranded-dna-viremia-after-allogeneic-hematopoietic-cell-transplantation
#16
Joshua A Hill, Bryan T Mayer, Hu Xie, Wendy M Leisenring, Meei-Li Huang, Terry Stevens-Ayers, Filippo Milano, Colleen Delaney, Keith R Jerome, Danielle M Zerr, Garrett Nichols, Michael Boeckh, Joshua T Schiffer
Background: Improved understanding of double stranded DNA (dsDNA) virus kinetics after hematopoietic cell transplantation (HCT) would facilitate development of therapeutic strategies. Methods: We tested weekly plasma samples from 404 patients through day 100 after allogeneic HCT for cytomegalovirus (CMV), human herpesvirus 6B (HHV-6B), HHV-6A, BK polyomavirus (BKV), adenovirus (AdV), and Epstein-Barr virus (EBV) using quantitative PCR. Episodes lasting ≤1 week were defined as blips and >1 week as persistent...
September 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28991252/population-pharmacokinetics-and-pharmacodynamics-of-mycophenolic-acid-using-the-prospective-data-in-patients-undergoing-hematopoietic-stem-cell-transplantation
#17
K Yoshimura, I Yano, T Yamamoto, M Kawanishi, Y Isomoto, A Yonezawa, T Kondo, A Takaori-Kondo, K Matsubara
Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used to suppress GvHD in patients undergoing hematopoietic stem cell transplantation (HCT). The purpose of this study was to construct a population pharmacokinetic and pharmacodynamic model in HCT patients for individualized MPA therapy. Blood samples were obtained from 49 HCT patients after starting MMF therapy. Population pharmacokinetic and pharmacodynamic parameters were obtained using the program NONMEM. MPA was described via a one-compartment model with a first-order elimination, and 30...
October 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28991250/assessment-of-trec-krec-and-telomere-length-in-long-term-survivors-after-allogeneic-hsct-the-role-of-gvhd-and-graft-source-and-evidence-for-telomere-homeostasis-in-young-recipients
#18
A Gaballa, A Norberg, A Stikvoort, J Mattsson, B Sundberg, M Uzunel, M Remberger, M Uhlin
Reconstitution of the adaptive immune system following allogeneic hematopoietic stem cell transplantation is crucial for beneficial outcome and is affected by several factors, such as GvHD and graft source. The impact of these factors on immune reconstitution has been thoroughly investigated during the early phase after transplantation. However, little is known about their long-term effect. Similarly, leukocyte telomere length (TL) shortening has been reported shortly after transplantation. Nevertheless, whether TL shortening continues in long-term aspect is still unsettled...
October 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28991247/long-term-prognosis-for-1-year-relapse-free-survivors-of-cd34-cell-selected-allogeneic-hematopoietic-stem-cell-transplantation-a-landmark-analysis
#19
C Cho, M Hsu, P Barba, M A Maloy, S T Avecilla, J N Barker, H Castro-Malaspina, S A Giralt, A A Jakubowski, G Koehne, R C Meagher, R J O'Reilly, E B Papadopoulos, D M Ponce, R Tamari, M R M van den Brink, J W Young, S M Devlin, M-A Perales
CD34+ cell selection significantly improves GvHD-free survival in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, specific information regarding long-term prognosis and risk factors for late mortality after CD34+ cell-selected allo-HSCT is lacking. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT for AML (n=164), ALL (n=33) or myelodysplastic syndrome (n=79). At 5 years' follow-up after the 1-year landmark (range 0...
October 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28991245/secondary-solid-cancer-following-hematopoietic-cell-transplantation-in-patients-with-thalassemia-major
#20
S Santarone, A Pepe, A Meloni, A Natale, L Pistoia, P Olioso, G Papalinetti, L Cuccia, A Spasiano, R Lisi, M Di Ianni, T Bonfini, P Accorsi, S Salvadori, F Papola, S Angelini, P Di Bartolomeo
Hematopoietic cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers (SSCs). The aim of this retrospective study was to compare the incidence of SSC in a monocentric cohort of thalassemia major (TM) patients (n=122) who received HCT versus an hematopoietic cell donor monocentric cohort (n=122) and versus a large multicenter cohort of age- and sex-matched TM patients (n=244) who received conventional therapy. With a median follow-up of 24 years, 8 transplanted patients were diagnosed with SSC at a median of 18 years after HCT and at a median age of 33 years...
October 9, 2017: Bone Marrow Transplantation
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