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https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#1
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28520526/kir3dl1-hl-a-b-subtypes-govern-acute-myelogenous-leukemia-relapse-after-hematopoietic-cell-transplantation
#2
Jeanette E Boudreau, Fabio Giglio, Ted A Gooley, Philip A Stevenson, Jean-Benoît Le Luduec, Brian C Shaffer, Raja Rajalingam, Lihua Hou, Carolyn Katovich Hurley, Harriet Noreen, Elaine F Reed, Neng Yu, Cynthia Vierra-Green, Michael Haagenson, Mari Malkki, Effie W Petersdorf, Stephen Spellman, Katharine C Hsu
Purpose Disease relapse remains a major challenge to successful outcomes in patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on leukemia cells-upregulated in the post-HCT environment-signals for NK cell inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and interrupts their antitumor activity. We hypothesized that varied strengths of inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA-B, would titrate NK reactivity against acute myelogenous leukemia (AML)...
May 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28423578/endothelial-microparticles-delivering-microrna-155-into-t-lymphocytes-are-involved-in-the-initiation-of-acute-graft-versus-host-disease-following-allogeneic-hematopoietic-stem-cell-transplantation
#3
Ran Zhang, Xiaoxiao Wang, Mei Hong, Ting Luo, Miaomiao Zhao, Haorui Shen, Jun Fang, Xiaojie Li, Sibin Zang, Ping Chen, Dimin Nie, Peng Zheng, Qiuling Wu, Linghui Xia
Endothelial microparticles (EMPs) upregulation has been observed in acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found that EMPs derived from TNF-α-stimulated human umbilical vein endothelial cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice were remarkably elevated and significantly higher than the levels in plasma...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414300/pd-l1-serves-as-a-double-agent-in-separating-gvl-from-gvhd
#4
Todd V Brennan, Yiping Yang
Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative treatment for a variety of hematologic malignancies due to the well-recognized graft-versus-leukemia/lymphoma (GVL) effect that is mediated by donor-derived alloreactive T cells. However, graft-versus-host disease (GVHD) is mediated by the same T cells and remains a significant clinical problem associated with substantial morbidity and mortality. In this issue of the JCI, Ni and colleagues used several murine models of GVHD to evaluate the effect of CD4+ T cell depletion on GVL versus GVHD and revealed that depletion of CD4+ T cells leads to the upregulation of PD-L1 by recipient tissues and donor CD8+ T cells...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414296/pd-l1-interacts-with-cd80-to-regulate-graft-versus-leukemia-activity-of-donor-cd8-t-cells
#5
Xiong Ni, Qingxiao Song, Kaniel Cassady, Ruishu Deng, Hua Jin, Mingfeng Zhang, Haidong Dong, Stephen Forman, Paul J Martin, Yuan-Zhong Chen, Jianmin Wang, Defu Zeng
Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28405514/regulatory-b-cells-promote-graft-versus-host-disease-prevention-and-maintain-graft-versus-leukemia-activity-following-allogeneic-bone-marrow-transplantation
#6
Yue Hu, Gan-Lin He, Xiang-Yu Zhao, Xiao-Su Zhao, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xue-Zhong Yu, Kai-Yan Liu, Ying-Jun Chang, Xiao-Jun Huang
Regulatory B cells (Bregs) are involved in the pathogenesis of graft-versus-host disease (GVHD). However, whether Bregs can alleviate acute GVHD without compromising graft-versus-leukemia (GVL) effects remains unclear. Here, we evaluated the role of Bregs in acute GVHD and GVL activity in both a mouse model and a clinical cohort study. In the acute GVHD mouse model, co-transplantation of Bregs prevents onset through inhibiting Th1 and Th17 differentiation and expanding regulatory T cells. In the GVL mouse model, Bregs contributed to the suppression of acute GVHD but had no adverse effect on GVL activity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28396161/isolated-extramedullary-relapse-of-acute-leukemia-after-allogeneic-stem-cell-transplantation-different-kinetics-and-better-prognosis-than-systemic-relapse
#7
Noga Shem-Tov, Francesco Saraceni, Ivetta Danylesko, Roni Shouval, Ronit Yerushalmi, Arnon Nagler, Avichai Shimoni
Allogeneic stem cell transplantation (SCT) is curative treatment in patients with acute leukemia and myelodysplastic syndrome. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary relapse (iEMR) after SCT is relatively rare and not well characterized. We performed a retrospective analysis of 566 consecutive patients with acute myeloid leukemia (n = 446) and acute lymphoblastic leukemia (ALL; n = 120) after SCT to study the incidence, risk factors, treatment options, and outcome of iEMR...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28375154/type-2-innate-lymphoid-cells-treat-and-prevent-acute-gastrointestinal-graft-versus-host-disease
#8
Danny W Bruce, Heather E Stefanski, Benjamin G Vincent, Trisha A Dant, Shannon Reisdorf, Hemamalini Bommiasamy, David A Serody, Justin E Wilson, Karen P McKinnon, Warren D Shlomchik, Paul M Armistead, Jenny P Y Ting, John T Woosley, Bruce R Blazar, Dietmar M W Zaiss, Andrew N J McKenzie, James M Coghill, Jonathan S Serody
Acute graft-versus-host disease (aGVHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGVHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. Thus, efforts to improve understanding of the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGVHD are needed. Here, we demonstrate, using murine models of allogeneic BMT, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#9
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28239380/development-of-three-different-nk-cell-subpopulations-during-immune-reconstitution-after-pediatric-allogeneic-hematopoietic-stem-cell-transplantation-prognostic-markers-in-gvhd-and-viral-infections
#10
Sabine Huenecke, Claudia Cappel, Ruth Esser, Verena Pfirrmann, Emilia Salzmann-Manrique, Sibille Betz, Eileen Keitl, Julia Banisharif-Dehkordi, Shahrzad Bakhtiar, Christoph Königs, Andrea Jarisch, Jan Soerensen, Evelyn Ullrich, Thomas Klingebiel, Peter Bader, Melanie Bremm
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56(++)CD16(-) (CD56(bright)), CD56(++)CD16(+) (CD56(intermediate=int)), and CD56(+)CD16(++) (CD56(dim)) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28183349/hif-1%C3%AE-inhibitor-echinomycin-reduces-acute-graft-versus-host-disease-and-preserves-graft-versus-leukemia-effect
#11
Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28159900/serum-mir-29a-is-upregulated-in-acute-graft-versus-host-disease-and-activates-dendritic-cells-through-tlr-binding
#12
Parvathi Ranganathan, Apollinaire Ngankeu, Nina C Zitzer, PierPaolo Leoncini, Xueyan Yu, Lucia Casadei, Kishore Challagundla, Dawn K Reichenbach, Sabrina Garman, Amy S Ruppert, Stefano Volinia, Jessica Hofstetter, Yvonne A Efebera, Steven M Devine, Bruce R Blazar, Muller Fabbri, Ramiro Garzon
Acute graft-versus-host disease (aGVHD) continues to be a frequent and devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT), posing as a significant barrier against the widespread use of HSCTs as a curative modality. Recent studies suggested serum/plasma microRNAs (miRs) may predict aGVHD onset. However, little is known about the functional role of circulating miRs in aGVHD. In this article, we show in two independent cohorts that miR-29a expression is significantly upregulated in the serum of allogeneic HSCT patients at aGVHD onset compared with non-aGVHD patients...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28139337/graft-versus-leukemia-effect-with-a-wt1-specific-t-cell-response-induced-by-azacitidine-and-donor-lymphocyte-infusions-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
Tatsunori Ishikawa, Nobuharu Fujii, Masahide Imada, Michinori Aoe, Yusuke Meguri, Tomoko Inomata, Hiromi Nakashima, Keiko Fujii, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Mitsune Tanimoto
BACKGROUND: Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. CASE REPORT: Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation...
January 27, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28133783/prognostic-impact-of-the-cd34-cd38-cell-burden-in-patients-with-acute-myeloid-leukemia-receiving-allogeneic-stem-cell-transplantation
#14
Madlen Jentzsch, Marius Bill, Deedra Nicolet, Sabine Leiblein, Karoline Schubert, Martina Pless, Ulrike Bergmann, Kathrin Wildenberger, Luba Schuhmann, Michael Cross, Wolfram Pönisch, Georg-Nikolaus Franke, Vladan Vucinic, Thoralf Lange, Gerhard Behre, Krzysztof Mrózek, Clara D Bloomfield, Dietger Niederwieser, Sebastian Schwind
In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects...
April 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28067665/selective-graft-versus-leukemia-depends-on-magnitude-and-diversity-of-the-alloreactive-t-cell-response
#15
Cornelis A M van Bergen, Simone A P van Luxemburg-Heijs, Liesbeth C de Wreede, Matthijs Eefting, Peter A von dem Borne, Peter van Balen, Mirjam H M Heemskerk, Arend Mulder, Fransiscus H J Claas, Marcelo A Navarrete, Wilhelmina M Honders, Caroline E Rutten, Hendrik Veelken, Inge Jedema, Constantijn J M Halkes, Marieke Griffioen, J H Frederik Falkenburg
Patients with leukemia who receive a T cell-depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28058217/review-of-allogeneic-hematopoietic-stem-cell-transplantation-with-reduced-intensity-conditioning-in-solid-tumors-excluding-breast-cancer
#16
REVIEW
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28027963/donor-lymphocyte-infusions-in-aml-and-mds-enhancing-the-graft-versus-leukemia-effect
#17
REVIEW
Guillermo Orti, Pere Barba, Laura Fox, Olga Salamero, Francesc Bosch, David Valcarcel
Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative therapy for many haematological malignancies. Its curative potential is mostly attributed to the graft-versus-leukemia effect (GvL), which is mainly driven by donor T-cells. Donor lymphocyte infusions (DLI), likewise a second allo-HCT, have become a standard approach to treat AML and MDS relapses post allo-HCT. Although DLI have been used in this setting for decades, its effectivity and toxicity are still unpredictable in many patients...
April 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28008806/role-of-il-26-cd26-cd4-t-cells-in-pulmonary-chronic-graft-versus-host-disease-and-treatment-with-caveolin-1-ig-fc-conjugate
#18
Kei Ohnuma, Ryo Hatano, Takumi Itoh, Noriaki Iwao, Nam H Dang, Chikao Morimoto
Obliterative bronchiolitis is the primary noninfectious pulmonary complication after allogeneic hematopoietic cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In our recent study, we identified a novel effect of IL-26, which is absent in rodents, on transplant related-obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood gradually exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27982314/immunotherapy-with-natural-killer-cells-a-possible-approach-for-the-treatment-of-acute-myeloid-leukemia-also-in-brazil
#19
Lúcia Silla
The allogeneic hematopoietic stem cell transplantation (HSCT) can cure intermediate and high-risk acute myeloid leukemia. Even with the development of strategies to reduce HSCT toxicity, this is still a complex treatment with high morbidity and mortality. Knowledge of the graft versus leukemia effect of HSCT has prepared the way for the development of Adoptive Immunotherapy or in vitro expansion of activated lymphocytes without alloreactivity, with subsequent intravenous infusion. The infusion of genetically modified T lymphocytes and haploidentical natural killer cells has been tested as an alternative to HSCT with very interesting results worldwide and in Brazil, as we not only have the technology of in vitro expansion of clinical grade lymphocytes available, but also do it according to the Good Manufacturing Practices that have been determined internationally...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27932143/report-from-the-first-and-second-spanish-killer-immunoglobulin-like-receptor-genotyping-workshops-external-quality-control-for-natural-killer-alloreactive-donor-selection-in-haploidentical-stem-cell-transplantation
#20
MULTICENTER STUDY
D Planelles, C Vilches, F González-Escribano, M Muro, R González-Fernández, F Sánchez, J Gonzalo Ocejo, A Eiras, J L Caro, E Palou, J A Campillo, M D de Juan, O Montes, A Balas, L Marín, A Torío, M Fernández-Arquero, C González-Roiz, A López-Vázquez, E Cisneros, C Abad-Molina, R López, M L Abad-Alastruey, C Serra, A M García-Alonso, J L Vicario
An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods...
November 2016: Transplantation Proceedings
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