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https://www.readbyqxmd.com/read/29769441/unique-features-and-clinical-importance-of-acute-alloreactive-immune-responses
#1
Charlotte F Inman, Suzy A Eldershaw, Joanne E Croudace, Nathaniel J Davies, Archana Sharma-Oates, Tanuja Rai, Hayden Pearce, Mirjana Sirovica, Y L Tracey Chan, Kriti Verma, Jianmin Zuo, Sandeep Nagra, Francesca Kinsella, Jane Nunnick, Rasoul Amel-Kashipaz, Charles Craddock, Ram Malladi, Paul Moss
Allogeneic stem cell transplantation (allo-SCT) can cure some patients with hematopoietic malignancy, but this relies on the development of a donor T cell alloreactive immune response. T cell activity in the first 2 weeks after allo-SCT is crucial in determining outcome, despite the clinical effects of the early alloreactive immune response often not appearing until later. However, the effect of the allogeneic environment on T cells is difficult to study at this time point due to the effects of profound lymphopenia...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29753837/status-of-nk-cell-recovery-in-day-21-bone-marrow-after-allogeneic-hematopoietic-stem-cell-transplantation-predicts-clinical-outcome
#2
Norimichi Hattori, Bungo Saito, Yohei Sasaki, Shotaro Shimada, So Murai, Maasa Abe, Yuta Baba, Megumi Watanuki, Shun Fujiwara, Yukiko Kawaguchi, Nana Arai, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Hirotsugu Ariizumi, Kouji Yanagisawa, Hiroshi Harada, Tsuyoshi Nakamaki
Rapid immune recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for clinical outcome prediction. In most studies, immune recovery after allo-HSCT has been monitored via peripheral blood. However, few reports regarding the status of absolute lymphocyte subsets in the bone marrow (BM) microenvironment have been undertaken. Therefore, we evaluated the clinical impact of immune recovery in the early period following allo-HSCT using BM samples. We showed that delayed natural killer (NK) cell recovery was independently associated with a poor prognosis for overall survival (hazard ratio (HR), 3...
May 10, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29753162/steroid-s-deleterious-effect-on-cmv-infection-rate-post-allo-sct-depends-on-pre-transplant-cmv-serostatus-of-donors-and-recipients
#3
María Suárez-Lledó, Núria Martínez-Cibrián, Gonzalo Gutiérrez-García, Veselka Dimova-Svetoslavova, Ma Angeles Marcos, Beatriz Martín-Antonio, Alejandra Martínez-Trillos, Neus Villamor, Laura Rosiñol, Carmen Martínez, Francesc Fernández-Avilés, Carolina García-Vidal, Álvaro Urbano-Ispizua, Montserrat Rovira
This study examined the impact of prednisone (PDN) on CMV infection after allogeneic stem cell transplantation (allo-SCT) according to donor (D) and recipient (R) CMV serostatus. Seventy-five patients underwent allo-SCT from June 2010 to July 2012. The risk of CMV infection according to D and R serostatus was defined as follows: high risk (HR) (D-/R+), intermediate risk (IR) (D+/R+ and D+/R-) and low risk (LR) (D-/R-). Forty-five patients (60%) developed CMV infection and forty-six patients (61%) received steroids (PDN ≥ 1 mg/kg/day) to treat acute Graft versus host disease (GvHD)...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29743501/a-phase-i-clinical-trial-with-ex-vivo-expanded-recipient-regulatory-t-cells-in-living-donor-kidney-transplants
#4
James M Mathew, Jessica H-Voss, Ann LeFever, Iwona Konieczna, Cheryl Stratton, Jie He, Xuemei Huang, Lorenzo Gallon, Anton Skaro, Mohammed Javeed Ansari, Joseph R Leventhal
There is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety of Tregs in hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis is that infusion(s) of Tregs may induce transplant tolerance thus avoiding long-term use of toxic immunosuppressive agents that cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation safety trial infusing billions of ex vivo expanded recipient polyclonal Tregs into living donor kidney transplant recipients...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740427/intestinal-microbiota-at-engraftment-influence-acute-graft-versus-host-disease-via-the-treg-th17-balance-in-allo-hsct-recipients
#5
Lijie Han, Hua Jin, Lizhi Zhou, Xin Zhang, Zhiping Fan, Min Dai, Qianyun Lin, Fen Huang, Li Xuan, Haiyan Zhang, Qifa Liu
Animal models have indicated that intestinal microbiota influence acute graft-versus-host disease (aGVHD) by modulating immune homeostasis. But, in humans, the mechanism by which the microbiota induces aGVHD remains unclear. In this study, we investigated the relationship between the intestinal microbiota and T cell subsets in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) to explore the mechanism by which microbiota induced aGVHD. Based on aGVHD, this study was categorized into two groups: grades II-IV aGVHD (aGVHD group, n  = 32) and grade 0-I aGVHD (non-aGVHD group, n  = 49)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29727487/kinetics-of-torque-teno-virus-dna-load-in-saliva-and-plasma-following-allogeneic-hematopoietic-stem-cell-transplantation
#6
Eliseo Albert, Ignacio Torres, Alberto Talaya, Estela Giménez, José Luis Piñana, Juan Carlos Hernández-Boluda, Daniele Focosi, Lisa Macera, Fabrizio Maggi, Carlos Solano, David Navarro
Plasma Torque Teno virus (TTV) DNA load directly correlates with the degree of T-cell immune reconstitution early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, the kinetics of oral TTV DNA shedding was examined to assess whether quantitation of TTV DNA load in saliva may either replace or complement that in plasma for predicting lymphocyte (ALC) reconstitution following engraftment. This prospective observational study enrolled 38 non-consecutive allo-HSCT recipients. Saliva and plasma specimens were collected at baseline (pre-transplant) and at around days +30, +50 and +90 after allo-HSCT...
May 4, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29724627/graft-failure-after-allogeneic-hematopoietic-stem-cell-transplantation
#7
REVIEW
Zehra Narli Ozdemir, Sinem Civriz Bozdağ
Graft failure is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Successful transplantation depends on the formation of engrafment, in which donor cells are integrated into the recipient's cell population. In this paper, we distinguish two different entities, graft failure (GF) and poor graft function (PGF), and review the current comprehensions of the interactions between the immune and hematopoietic compartments in these conditions...
April 18, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29720488/recommendations-for-managing-pd-1-blockade-in-the-context-of-allogeneic-hct-in-hodgkin-lymphoma-taming-a-necessary-evil
#8
Charles Herbaux, Reid Merryman, Steven Devine, Philippe Armand, Roch Houot, Franck Morschhauser, Bradley Haverkos
PD-1 blockade is an effective therapy in relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) who have relapsed after or are ineligible for autologous hematopoietic cell transplantation (HCT). While single-agent anti-PD-1 monoclonal antibodies (mAbs) are associated with high response rates and durable remissions, available results to date suggest that a large majority of patients will eventually progress on therapy. Many of these patients are potential candidates for allogeneic HCT (allo-HCT) after receiving anti-PD-1 mAbs, and allo-HCT remains for now the only treatment with demonstrated curative potential in this setting...
May 2, 2018: Blood
https://www.readbyqxmd.com/read/29682375/myeloid-sarcoma-after-allogenic-stem-cell-transplantation-for-acute-myeloid-leukemia-successful-consolidation-treatment-approaches-in-two-patients
#9
Silje Johansen, Hilde Kollsete Gjelberg, Aymen Bushra Ahmed, Øystein Bruserud, Håkon Reikvam
Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI)...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29679773/distinctive-infectious-complications-in-patients-with-central-nervous-system-lymphoma-undergoing-thiotepa-busulfan-and-cyclophosphamide-tbc-conditioned-autologous-stem-cell-transplantation
#10
Michael Scordo, Sejal M Morjaria, Eric R Littmann, Ankush Bhatia, Helen H Chung, Molly Maloy, Lisa M DeAngelis, Sergio A Giralt, Ying Taur, Craig S Sauter
We investigated the incidence of viral, fungal, bacterial, and parasitic infections observed in 57 patients with central nervous system lymphoma (CNSL) after TBC-ASCT and 79 patients with systemic NHL after traditional BEAM-ASCT. Twenty of 57 (35%) TBC-ASCT patients had detectable viremia with human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), adenovirus (ADV), or BK virus (BKV), versus 9 of 79 (11%) BEAM-ASCT patients. Nine TBC-ASCT patients had clinically relevant viral infections (4 HHV-6, 2 CMV, 1 ADV, 2 BKV), versus 0 in the BEAM-ASCT group...
April 18, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29678809/delayed-immune-reconstitution-after-allogeneic-transplantation-increases-the-risks-of-mortality-and-chronic-gvhd
#11
Nelli Bejanyan, Claudio G Brunstein, Qing Cao, Aleksandr Lazaryan, Xianghua Luo, Julie Curtsinger, Rohtesh S Mehta, Erica Warlick, Sarah A Cooley, Bruce R Blazar, Jeffrey S Miller, Daniel Weisdorf, John E Wagner, Michael R Verneris
Slow immune reconstitution is a major obstacle to the successful use of allogeneic hematopoietic cell transplantation (allo-HCT). As matched sibling donor (MSD) allo-HCT is regarded as the gold standard, we evaluated the pace of immune reconstitution in 157 adult recipients of reduced-intensity conditioning followed by MSD peripheral blood HCT (n = 68) and compared these to recipients of umbilical cord blood (UCB; n = 89). At day 28, UCB recipients had fewer natural killer (NK) cells than MSD recipients, but thereafter, NK cell numbers (and their subsets) were higher in UCB recipients...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29575692/effect-of-the-in-vivo-application-of-granulocyte-colony-stimulating-factor-on-nk-cells-in-bone-marrow-and-peripheral-blood
#12
Xing-Xing Yu, Ting-Ting Han, Ling-Ling Xu, Ying-Jun Chang, Xiao-Jun Huang, Xiang-Yu Zhao
Granulocyte colony-stimulating factor (G-CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo-HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor-derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post-allo-HSCT. The aim of this study was to evaluate the effect of G-CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post-G-CSF in vivo application...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29555188/untangling-galectin-driven-regulatory-circuits-in-autoimmune-inflammation
#13
REVIEW
Marta A Toscano, Verónica C Martínez Allo, Anabela M Cutine, Gabriel A Rabinovich, Karina V Mariño
Although progress has been made in understanding the mechanisms implicated in the pathogenesis of autoimmune inflammation, studies aimed at identifying the mediators of these pathways will be necessary to develop more selective therapies. Galectins, a family of glycan-binding proteins, play central roles in immune cell homeostasis. Whereas some members of this family trigger regulatory programs that promote resolution of inflammation, others contribute to perpetuate autoimmune processes. We discuss the roles of endogenous galectins and their specific glycosylated ligands in shaping autoimmune responses by fueling, extinguishing, or rewiring immune circuits...
April 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29552016/-in-utero-exposure-to-exosomal-and-b-cell-alloantigens-lessens-alloreactivity-of-recipients-lymphocytes-rather-than-confers-allograft-tolerance
#14
Jeng-Chang Chen, Liang-Shiou Ou, Cheng-Chi Chan, Ming-Ling Kuo, Li-Yun Tseng, Hsueh-Ling Chang
According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29552004/timing-determination-of-invasive-fungal-infection-prophylaxis-according-to-immune-function-in-hsct-patients
#15
Jiexian Ma, Yingwei Hu, Min Wu, Xiaoqin Wang, Yanhui Xie
Patients who receive a hematopoietic stem cell transplantation (HSCT) exhibit an immune defect after recovering from neutropenia. The current guidelines do not recommend fungal prophylaxis in these patients, except for grades III to IV GVHD in HSCT. Thus, the timing for the initiation and cessation of IFI prophylaxis in immune-compromised patients remains a challenging endeavor. We retrospectively analyzed patients who received auto or allo-HSCT and monitored their immune function after recovering from neutropenia by measuring the levels of IgG, IgA, IgM, as well as the number of T, B, NK cells...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29545911/impact-on-early-outcomes-and-immune-reconstitution-of-high-dose-post-transplant-cyclophosphamide-vs-anti-thymocyte-globulin-after-reduced-intensity-conditioning-peripheral-blood-stem-cell-allogeneic-transplantation
#16
Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29541991/rapid-reconstitution-of-nk1-cells-after-allogeneic-transplantation-is-associated-with-a-reduced-incidence-of-graft-versus-host-disease
#17
Xingxing Yu, Lingling Xu, Yingjun Chang, Xiaojun Huang, Xiangyu Zhao
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT...
March 9, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29540850/elevated-soluble-human-leukocyte-antigen-g-levels-in-patients-after-allogeneic-stem-cell-transplantation-are-associated-with-less-severe-acute-and-chronic-graft-versus-host-disease
#18
Lambros Kordelas, Fabiola da Silva Nardi, Bettina Wagner, Markus Ditschkowski, Tobias Liebregts, Monika Lindemann, Falko M Heinemann, Peter A Horn, Dietrich W Beelen, Vera Rebmann
HLA-G is a non-classical class I molecule which induces tolerance in allogeneic situations by inhibition of cytotoxic NK and CD8 + T cells and by induction of regulatory T cells. Concordantly, in solid organ transplantation HLA-G is associated with a lower risk for acute and chronic rejection, whereas its role in allogeneic stem cell transplantation (allo-SCT) is less established. We here present detailed analyses of HLA-G-levels in patients after allo-SCT showing a correlation of elevated soluble HLA-G (sHLA-G) levels with less severe acute (p = 0...
March 14, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29505821/early-reconstitution-of-nk-and-%C3%AE-%C3%AE-t-cells-and-its-implication-for-the-design-of-post-transplant-immunotherapy
#19
Moniek A de Witte, Dhifaf Sarhan, Zachary Davis, Martin Felices, Daniel A Vallera, Peter Hinderlie, Julie Curtsinger, Sarah Cooley, John Wagner, Jurgen Kuball, Jeffrey S Miller
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Natural killer (NK) cells and γδ T cells reconstitute early after allo-HSCT, contribute to tumor immunosurveillance via major histocompatibility complex-independent mechanisms and do not induce graft-versus-host disease. Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HSCT (MSD/MUD-HSCT) and umbilical cord blood-HSCT (UCB-HSCT)...
March 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29500170/transplant-strategies-in-relapsed-refractory-hodgkin-lymphoma
#20
REVIEW
Gunjan L Shah, Craig H Moskowitz
The majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy. However, high-dose therapy with autologous hematopoietic cell transplant (AHCT) allows for the cure of an additional portion of patients with relapsed or primary refractory disease. Positron emission tomography-negative complete remission before AHCT is critical for long-term disease control. Several salvage options are available with comparable response rates, and the choice can be dependent of comorbidities and logistics. Radiation therapy can also improve the remission rate and is an important therapeutic option for selected patients...
April 12, 2018: Blood
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