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https://www.readbyqxmd.com/read/29691471/baricitinib-induced-blockade-of-interferon-gamma-receptor-and-interleukin-6-receptor-for-the-prevention-and-treatment-of-graft-versus-host-disease
#1
Jaebok Choi, Matthew L Cooper, Karl Staser, Kidist Ashami, Kiran R Vij, Bing Wang, Lynne Marsala, Jessica Niswonger, Julie Ritchey, Bader Alahmari, Samuel Achilefu, Ikuo Tsunoda, Mark A Schroeder, John F DiPersio
The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are derived from the graft-versus-leukemia (GvL) effects of the procedure. There is a strong association between the GvL effects and graft-versus-host disease (GvHD), a major life-threatening complication of allo-HSCT. The limiting of GvHD while maintaining the GvL effect remains the goal of allo-HSCT. Therefore, identifying optimal therapeutic targets to selectively suppress GvHD while maintaining the GvL effects represents a significant unmet medical need...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29678553/recipient-and-donor-cells-in-the-graft-versus-solid-tumor-effect-it-takes-two-to-tango
#2
REVIEW
Isabelle Dierckx de Casterlé, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation (alloHSCT) produces -similar to the long-established graft-versus-leukemia effect- graft-versus-solid-tumor effects. Clinical trials reported response rates of up to 53%, occurring mostly but not invariably in association with full donor chimerism and/or graft-versus-host disease. Although donor-derived T cells are considered the principal effectors of anti-tumor immunity after alloHSCT or donor leukocyte infusion (DLI), growing evidence indicate that recipient-derived immune cells may also contribute...
April 12, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29649617/reversal-of-t-cell-exhaustion-by-the-first-donor-lymphocyte-infusion-is-associated-with-the-persistently-effective-anti-leukemic-responses-in-patients-with-relapsed-aml-after-allo-hsct
#3
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Donor lymphocyte infusion is an effective approach to treat acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly improves the survival of relapsed patients. However, the mechanism of an effective anti-leukemic response following DLI in AML relapse remains elusive. Here, we investigated the role of T cell exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients with the first AML relapse and 41 non-relapsed AML controls after allo-HSCT and determined whether DLI exerts effective anti-leukemic effects by reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes and functions of T cells using flow cytometry...
April 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29577208/hematopoietic-stem-cell-transplantation-for-adult-philadelphia-negative-acute-lymphoblastic-leukemia-in-the-first-complete-remission-in-the-era-of-minimal-residual-disease
#4
REVIEW
Christianne Bourlon, Dennis Lacayo-Leñero, Sergio I Inclán-Alarcón, Roberta Demichelis-Gómez
PURPOSE OF REVIEW: The purpose of this review is to discuss the potential role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia-negative (Ph- ) adult acute lymphoblastic leukemia (ALL) in first complete remission (CR1) in the era of minimal residual disease (MRD). RECENT FINDINGS: Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT...
March 26, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29550628/current-allogeneic-hsct-for-pediatric-all-success-failure-and-future-perspectives-a-single-center-experience-2008-2016
#5
Asaf D Yanir, Caridad A Martinez, Ghadir Sasa, Kathryn Leung, Stephen Gottschalk, Bilal Omer, Nabil Ahmed, Meenakshi Hegde, Jo Eunji, Hao Liu, Helen E Heslop, Malcolm K Brenner, Robert A Krance, Swati Naik
Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed Acute Lymphoblastic Leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T-cell depletion used, and consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes between different donor types...
March 14, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29549412/donor-recipient-killer-immunoglobulin-like-receptor-kir-genotype-matching-has-a-protective-effect-on-chronic-graft-versus-host-disease-and-relapse-incidence-following-hla-identical-sibling-hematopoietic-stem-cell-transplantation
#6
Ugur Sahin, Klara Dalva, Funda Gungor, Celalettin Ustun, Meral Beksac
Impact of donor-recipient killer immunoglobulin-like receptor (KIR) gene-gene matching on transplant outcomes is still inconclusive. Recent data suggest that killer cell immunoglobulin-like receptor (KIR) regulated natural killer cell (NK cell) activity may contribute to graft versus leukemia (GvL) effects and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case-control study aims to evaluate the effects of both aKIR and iKIR donor-recipient genotype matching on the outcomes of T cell replete HLA-identical sibling allo-HSCTs in a homogenous young patient population with myeloid leukemias...
March 16, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29549293/prognostic-role-of-kir-genes-and-hla-c-after-hematopoietic-stem-cell-transplantation-in-a-patient-cohort-with-acute-myeloid-leukemia-from-a-consanguineous-community
#7
Ameera Gaafar, Atia Sheereen, Fahad Almohareb, Abdelmoneim Eldali, Naeem Chaudhri, Said Y Mohamed, Amr Hanbali, Marwan Shaheen, Feras Alfraih, Riad El Fakih, Alia Iqneibi, Riad Youniss, Tusneem Elhassan, Shahrukh Hashmi, Mahmud Aljurf, Khalid Alhussein
NK cell activity is tuned by a balance of activating and inhibitory signals transmitted via their respective receptors, including killer immunoglobulin-like receptors (KIRs). The impact of NK cells on graft-versus-leukemia following hematopoietic stem cell transplantation (HSCT) is well established. These effects sometimes lead to GvHD. The link between KIR/HLA interaction and GvHD remains unclear. Herein, we studied the impact of the KIR/HLA interaction on HSCT outcomes in a longitudinal follow-up study of a highly consanguineous HLA-matched related cohort...
March 16, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29547016/the-current-and-future-role-of-stem-cells-in-myelodysplastic-syndrome-therapies
#8
Guido Kobbe, Thomas Schroeder, Rainer Haas, Ulrich Germing
Allogeneic blood stem cell transplantation (aBSCT) still is the only curative therapy for patients with myelodysplastic syndromes. While it carries the hope for cure for some patients, it may result in severe toxicity and death from complications or recurrent disease in others. Recent developments have improved patient and donor selection as well as technical aspects of the transplant procedure and post-transplant care, including early detection and treatment of relapse. Areas covered: This review will discuss current stratification tools to identify suitable patients, donors and transplant techniques...
May 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29500069/generation-of-alloreactivity-reduced-donor-lymphocyte-products-retaining-memory-function-by-fully-automatic-depletion-of-cd45ra-positive-cells
#9
Nina Müller, Katharina Landwehr, Kirsten Langeveld, Joanna Stenzel, Walter Pouwels, Menno A W G van der Hoorn, Erhard Seifried, Halvard Bonig
BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+ ) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution...
April 2018: Cytotherapy
https://www.readbyqxmd.com/read/29483082/inhibition-of-the-ire-1%C3%AE-xbp-1-pathway-prevents-chronic-gvhd-and-preserves-the-gvl-effect-in-mice
#10
Steven D Schutt, Yongxia Wu, Chih-Hang Anthony Tang, David Bastian, Hung Nguyen, M Hanief Sofi, MengMeng Zhang, Chen Liu, Kris Helke, Carole Wilson, Lynn M Schnapp, Juan R Del Valle, Chih-Chi Andrew Hu, Xue-Zhong Yu
Hematopoietic stem cell transplantation (HCT) is a curative procedure for hematological malignancies, but chronic graft-versus-host disease (cGVHD) remains a major complication after allogeneic HCT. Because donor B cells are essential for cGVHD development and B cells are sensitive to endoplasmic reticulum (ER) stress, we hypothesized that the IRE-1α/XBP-1 pathway is required for B-cell activation and function and for the development of cGVHD. To test this hypothesis, we used conditional knock-out mice deficient of XBP-1 specifically in B cells...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29477343/t-cell-exhaustion-characterized-by-compromised-mhc-class-i-and-ii-restricted-cytotoxic-activity-associates-with-acute-b-lymphoblastic-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#11
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Acute B lymphoblastic leukemia (B-ALL) relapse contributes predominantly to the mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanism of B-ALL relapse after allo-HSCT remains unknown. The eradication of leukemia after allo-HSCT largely relies on graft-versus-leukemia (GVL) effects mediated by donor T cells. T cell exhaustion, characterized by the increased expression of inhibitory receptors and impaired function, may suppress GVL effects. In this study, we evaluated whether T cell exhaustion was involved in B-ALL relapse after allo-HSCT...
May 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29470425/major-histocompatibility-complex-and-hematopoietic-stem-cell-transplantation-beyond-the-classical-hla-polymorphism
#12
REVIEW
Alice Bertaina, Marco Andreani
Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative treatment for many patients with hematological malignant or non-malignant disorders. Evaluation of potential donors for HSCT includes a rigorous assessment of the human leukocyte antigens (HLA) match status of family members, and the identification of suitable unrelated donors. Genes encoding transplantation antigens are placed both within and outside the major histocompatibility complex (MHC). The human MHC is located on the short arm of chromosome 6 and contains a series of genes encoding two distinct types of highly polymorphic cell surface glycoproteins...
February 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29443409/cellular-collection-by-apheresis
#13
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/29431743/sorafenib-promotes-graft-versus-leukemia-activity-in-mice-and-humans-through-il-15-production-in-flt3-itd-mutant-leukemia-cells
#14
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 Shah, 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...
March 2018: Nature Medicine
https://www.readbyqxmd.com/read/29390324/successful-treatment-with-allogeneic-stem-cell-transplantation-followed-by-dli-and-tkis-for-e6a2-bcr-abl-positive-acute-myeloid-leukaemia-a-case-report-and-literature-review
#15
REVIEW
Yasuhiko Harada, Satoshi Nishiwaki, Takumi Sugimoto, Koichi Onodera, Tatsunori Goto, Takahiko Sato, Sonoko Kamoshita, Naomi Kawashima, Aika Seto, Shingo Okuno, Satomi Yamamoto, Toshihiro Iwasaki, Yukiyasu Ozawa, Koichi Miyamura, Yoshiki Akatsuka, Isamu Sugiura
RATIONALE: Patients with the e6a2 BCR-ABL transcript, 1 of the atypical transcripts, have been reported to have a poor prognosis, and allogeneic stem cell transplantation (ASCT) can be considered as additional therapy. However, long-term survival after ASCT for this disease is rare. PATIENT CONCERNS: This report concerns a 55-year-old female patient with e6a2 BCR-ABL-positive acute myeloid leukemia including the outcome of ASCT followed by donor lymphocyte infusion (DLI)...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29382747/targeting-jak2-reduces-gvhd-and-xenograft-rejection-through-regulation-of-t-cell-differentiation
#16
Brian C Betts, David Bastian, Supinya Iamsawat, Hung Nguyen, Jessica L Heinrichs, Yongxia Wu, Anusara Daenthanasanmak, Anandharaman Veerapathran, Alison O'Mahony, Kelly Walton, Jordan Reff, Pedro Horna, Elizabeth M Sagatys, Marie C Lee, Jack Singer, Ying-Jun Chang, Chen Liu, Joseph Pidala, Claudio Anasetti, Xue-Zhong Yu
Janus kinase 2 (JAK2) signal transduction is a critical mediator of the immune response. JAK2 is implicated in the onset of graft-versus-host disease (GVHD), which is a significant cause of transplant-related mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Transfer of JAK2-/- donor T cells to allogeneic recipients leads to attenuated GVHD yet maintains graft-versus-leukemia. Th1 differentiation among JAK2-/- T cells is significantly decreased compared with wild-type controls. Conversely, iTreg and Th2 polarization is significantly increased among JAK2-/- T cells...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29374826/hematopoietic-stem-cell-transplantation-for-acute-myeloid-leukemia
#17
REVIEW
Akiyoshi Takami
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields a high rate of curability for acute myeloid leukemia (AML), it is also associated with transplant-related morbidity and mortality (TRM). The risk and severity of TRM increase with the use of an alternative donor graft in the absence of an HLA-matched sibling donor (MSD). With the declining birthrate and aging of the population, the numbers of patients with an MSD are decreasing, and alternative donor transplants, including the post-transplant cyclophosphamide method using haplo-identical donors, are increasing...
May 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29367429/flt-3l-expansion-of-recipient-cd8%C3%AE-dendritic-cells-deletes-alloreactive-donor-t-cells-and-represents-an-alternative-to-post-transplant-cyclophosphamide-for-the-prevention-of-gvhd
#18
Kate Markey, Rachel D Kuns, Daniel J Browne, Kate H Gartlan, Renee J Robb, J Paulo Martins, Andrea S Henden, Simone A Minnie, Melody Cheong, Motoko Koyama, Mark J Smyth, Raymond J Steptoe, Gabrielle Belz, Thomas Brocker, Mariapia A Degli-Esposti, Steven W Lane, Geoffrey R Hill
PURPOSE: Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunological graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD. EXPERIMENTAL DESIGN: We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DC in controlling donor T cell mediated GVHD and GVL...
January 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29362503/alloantigen-expression-on-malignant-cells-and-healthy-host-tissue-influences-graft-versus-tumor-reactions-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
Stella Robert, Jörn C Albring, Karin Frebel, Corinna Opitz, Jennifer Urh, Claudia Wolf, Christine Heinrich, Wolfgang E Berdel, Matthias Stelljes
Durable remissions of hematological malignancies regularly observed following allogeneic hematopoietic stem cell transplantation (aHSCT) are due to the conditioning regimen, as well as an immunological phenomenon called graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. The development of GVL is closely linked to graft-versus-host disease (GVHD), the main side effect associated with aHSCT. Both, GVHD and GVL are mediated by donor T cells that are initially activated by antigen-presenting cells that present recipient-derived alloantigens in the context of either matched or mismatched MHC class I molecules...
January 23, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29358176/the-potential-role-of-%C3%AE-%C3%AE-t-cells-after-allogeneic-hct-for-leukemia
#20
REVIEW
Rupert Handgretinger, Karin Schilbach
Allogeneic hematopoetic stem cell transplantation (HCT) offers an option for patients with hematologic malignancies, in whom conventional standard therapies failed or are not effective enough to cure the disease. Successful HCT can restore functional hematopoiesis and immune function, and the new donor-derived immune system can exert a graft-versus-leukemia (GVL) effect. However, allogenic HCT can also be associated with serious risks for transplantation-related morbidities or mortalities such as graft-versus-host disease (GVHD) or life-threatening infectious complications...
March 8, 2018: Blood
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