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Graft vs host disease

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https://www.readbyqxmd.com/read/28734876/t-cell-depletion-as-an-alternative-approach-for-patients-55-years-undergoing-allogeneic-stem-cell-transplantation-as-curative-therapy-for-hematologic-malignancies
#1
Ann A Jakubowski, Erica Petrlik, Molly Maloy, Patrick Hilden, Esperanza Papadopoulos, James W Young, Farid Boulad, Hugo Castro-Malaspina, Roni Tamari, Parastoo B Dahi, Jenna Goldberg, Guenther Koehne, Miguel-Angel Perales, Craig S Sauter, Richard J O'Reilly, Sergio Giralt
T cell depleted allogeneic hematopoietic stem cell transplantation (TCD HSCT) is curative treatment for hematologic malignancies in adults, shown to reduce graft vs. host disease (GVHD) without increased relapse. We retrospectively reviewed a single center, 11yr experience of 214 patients ≥55yrs to determine tolerability and efficacy in the older adult. The majority (70%) had myeloid diseases and most acute leukemias were in remission. Median age was 61 yrs with related and unrelated donors > 8/10 HLA matched...
July 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28733533/similar-outcomes-after-haploidentical-transplantation-with-post-transplant-cyclophosphamide-versus-hla-matched-transplantation-a-meta-analysis-of-case-control-studies
#2
Zhenyang Gu, Li Wang, Lei Yuan, Wenrong Huang, Meng Li, Lixun Guan, Qingyi Wang, Zhe Gao, Shasha Zhao, Lan Luo, Feiyan Wang, Nan Yang, Daihong Liu, Jon C Aster, Chunji Gao
BACKGROUND: Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT. METHODS: A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733186/easix-in-patients-with-acute-graft-versus-host-disease-a-retrospective-cohort-analysis
#3
Thomas Luft, Axel Benner, Sonata Jodele, Christopher E Dandoy, Rainer Storb, Ted Gooley, Brenda M Sandmaier, Natalia Becker, Aleksandar Radujkovic, Peter Dreger, Olaf Penack
BACKGROUND: Endothelial dysfunction links thrombotic microangiopathy to steroid-refractory graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation. We aimed to assess if the simple formula-lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (10(9) cells per L)-termed the Endothelial Activation and Stress Index (EASIX), might be valuable for the prediction of death in patients with acute GVHD after allogeneic stem-cell transplantation. METHODS: For this retrospective analysis, we analysed a training cohort (in Germany) and three validation cohorts (in Germany and the USA) of patients with acute GVHD who had received consecutive allogeneic stem-cell transplantation...
July 18, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28720679/potential-for-monitoring-gut-microbiota-for-diagnosing-infections-and-graft-versus-host-disease-in-cancer-and-stem-cell-transplant-patients
#4
Andrew Y Koh
BACKGROUND: Gut microbiota, the collective community of microorganisms inhabiting the intestine, have been shown to provide many beneficial functions for the host. Recent advances in next-generation sequencing and advanced molecular biology approaches have allowed researchers to identify gut microbiota signatures associated with disease processes and, in some cases, establish causality and elucidate underlying mechanisms. CONTENT: This report reviews 3 commonly used methods for studying the gut microbiota and microbiome (the collective genomes of the gut microorganisms): 16S rRNA gene sequencing, bacterial group or species-specific quantitative polymerase chain reaction (qPCR), and metagenomic shotgun sequencing (MSS)...
July 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#5
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28712934/donor-lymphocyte-infusions-used-to-treat-mixed-chimeric-and-high-risk-patient-populations-in-the-relapsed-and-non-relapsed-settings-after-allogeneic-transplant-for-hematologic-malignancies-are-associated-with-high-5-year-survival-if-persistent-full-donor-chimerism
#6
Lauren E Caldemeyer, Luke P Akard, John R Edwards, Anand Tandra, Dawn R Wagenknecht, Michael J Dugan
Mixed chimerism (MC), a persistent or increasing number of host cells after allogeneic hematopoietic stem cell transplant (HSCT), is a predictor of disease relapse. Donor lymphocyte infusions (DLI) have the potential to enhance the graft vs. malignancy (GvM) effect, reducing the risk of relapse in patients with MC. Hence, in addition to utilizing DLI in the relapsed setting, there is a motivation to pursue pre-emptive DLI for patients in complete remissions (CR) after HSCT. To assess the safety and efficacy of DLI, records of 86 patients who received DLI between 2003 and 2015 at a single institution were studied retrospectively...
July 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28710997/dynamics-of-torque-teno-virus-plasma-dnaemia-in-allogeneic-stem-cell-transplant-recipients
#7
Eliseo Albert, Carlos Solano, Tania Pascual, Ignacio Torres, Lisa Macera, Daniele Focosi, Fabrizio Maggi, Estela Giménez, Paula Amat, David Navarro
BACKGROUND: Torque Teno virus (TTV) plasma DNA load directly correlate with the level of immunosuppresion in different clinical settings. It is uncertain whether this may be the case in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). OBJECTIVES: We characterized the dynamics of TTV DNAemia in patients undergoing T-cell replete allo-SCT. STUDY DESIGN: Retrospective single-center observational study including 72 allo-HSCT patients...
July 8, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28708597/mri-based-evaluation-of-multiorgan-iron-overload-is-a-predictor-of-adverse-outcomes-in-pediatric-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#8
Natalia Maximova, Massimo Gregori, Giulia Boz, Roberto Simeone, Davide Zanon, Giulia Schillani, Floriana Zennaro
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705454/efficacy-of-two-different-doses-of-rabbit-anti-t-lymphocyte-globulin-to-prevent-graft-versus-host-disease-in-children-with-haematological-malignancies-transplanted-from-an-unrelated-donor-a-multicentre-randomised-open-label-phase-3-trial
#9
Franco Locatelli, Maria Ester Bernardo, Alice Bertaina, Carla Rognoni, Patrizia Comoli, Attilio Rovelli, Andrea Pession, Franca Fagioli, Claudio Favre, Edoardo Lanino, Giovanna Giorgiani, Pietro Merli, Daria Pagliara, Arcangelo Prete, Marco Zecca
BACKGROUND: Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). METHODS: We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci...
July 10, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28688097/b-lymphocyte-chemoattractant-cxcl13-is-an-indicator-of-acute-gastrointestinal-gvhd-in-murine-model
#10
Yigeng Cao, Xiaoyi Qin, Na Wang, Erlie Jiang, Mingzhe Han, Yongyong Ma, Bin Liang, Kaiyan Yang, Kang Yu, Haige Ye
Gastrointestinal acute graft-vs.-host disease (GI aGVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation and is a major cause of morbidity and mortality. In addition, GI aGVHD is often clinically indistinguishable from other causes of GI dysfunction such as conditioning regimen toxicity, infections, or medications, which complicates the diagnosis. Thus, specific biomarkers are needed to help improve diagnosis and obtain a deeper understanding of the cytokine changes in GI aGVHD...
July 7, 2017: Inflammation
https://www.readbyqxmd.com/read/28676100/superior-gvhd-free-relapse-free-survival-for-g-bm-to-g-pbsc-grafts-is-associated-with-higher-mdscs-content-in-allografting-for-patients-with-acute-leukemia
#11
Qian Fan, Hui Liu, Xinquan Liang, Ting Yang, Zhiping Fan, Fen Huang, Yiwen Ling, Xin Liao, Li Xuan, Na Xu, Xiaojun Xu, Jieyu Ye, Qifa Liu
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1)...
July 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28670436/bridging-to-transplant-with-azacitidine-for-myelodysplastic-syndrome-and-acute-myeloid-leukemia-reduces-the-incidence-of-acute-graft-versus-host-disease
#12
Koichi Murakami, Hironori Ueno, Takashi Okabe, Toshiya Kagoo, Saigen Boku, Takahiro Yano, Akihiro Yokoyama
Allogeneic stem cell transplantation (allo-SCT) is the only curative option for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Azacitidine (AZA) has a good toxicity profile compared with intensive chemotherapy and can be considered a pre-transplant regimen in elderly patients and in patients with comorbidities. To investigate the impact of pre-transplant AZA on patient outcome after allo-SCT, we conducted a retrospective analysis of AZA pre-treatment followed by allo-SCT in patients with high-risk MDS and AML...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#13
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28632323/clinical-outcomes-of-hla-dpb1-mismatches-in-10-10-hla-matched-unrelated-donor-recipient-pairs-undergoing-allogeneic-stem-cell-transplant
#14
Ann M Moyer, Shahrukh K Hashmi, Cynthia M Kroning, Walter K Kremers, Steven R De Goey, Mrinal Patnaik, Mark Litzow, Dennis A Gastineau, William J Hogan, Eapen K Jacob, Justin D Kreuter, Laurie L Wakefield, Manish J Gandhi
OBJECTIVE: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. METHODS: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1 and DQB1 loci (10/10)...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28608529/comparison-of-the-cellex%C3%A2-and-uvar-xts%C3%A2-closed-system-extracorporeal-photopheresis-devices-in-the-treatment-of-chronic-graft-versus-host-disease
#15
Robert M Whittle, Helen Denney, Andrew D Chantry, Arun Alfred, Peter C Taylor
Extracorporeal Photopheresis (ECP) is a cellular immunotherapy frequently used for steroid-refractory graft-versus-host disease (GVHD). Chronic GVHD (cGVHD), response to ECP is associated with survival benefit. The UVAR-XTS(TM) system and the more recently developed CELLEX(TM) device (both Therakos(TM) ) are the mainstay for ECP-delivery in the UK and US. No comparison of treatment outcomes has been reported. We retrospectively compared cGVHD response and steroid reduction and withdrawal in patients treated exclusively over 12 months with either the XTS (n = 51) or CELLEX (n = 50)...
June 13, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28607133/loss-of-thymic-innate-lymphoid-cells-leads-to-impaired-thymopoiesis-in-experimental-graft-vs-host-disease
#16
Jarrod A Dudakov, Anna M Mertelsmann, Margaret H O'Connor, Robert R Jenq, Enrico Velardi, Lauren F Young, Odette M Smith, Richard L Boyd, Marcel R M van den Brink, Alan M Hanash
Graft vs. host disease (GVHD) and post-transplant immunodeficiency are frequently related complications of allogeneic hematopoietic transplantation. Alloreactive donor T cells can damage thymic epithelium, thus limiting new T cell development. While the thymus has a remarkable capacity to regenerate after injury, endogenous thymic regeneration is impaired in GVHD. The mechanisms leading to this regenerative failure are largely unknown. Here we demonstrate in experimental mouse models that GVHD results in depletion of intrathymic group 3 innate lymphoid cells (ILC3s) necessary for thymic regeneration...
June 12, 2017: Blood
https://www.readbyqxmd.com/read/28602890/posterior-reversible-encephalopathy-syndrome-after-hematopoietic-cell-transplantation-in-children-with-hemoglobinopathies
#17
Javid Gaziev, Simone Marziali, Katia Paciaroni, Antonella Isgrò, Francesca Di Giuliano, Giorgia Rossi, Marco Marziali, Gioia De Angelis, Cecilia Alfieri, Michela Ribersani, Marco Andreani, Maria Giuseppina Palmieri, Fabio Placidi, Andrea Romigi, Francesca Izzi, Roberto Floris, Nicola Biagio Mercuri
Posterior reversible encephalopathy syndrome (PRES) is a serious adverse event associated with calcineurin inhibitors used for graft-versus-host disease (GVHD) prophylaxis. We compared the incidence of PRES in children with thalassemia (n = 222, 1.4 to 17.8 years old) versus sickle cell disease (SCD; n = 59, 2 to 17 years old) who underwent hematopoietic cell transplantation from HLA-matched siblings or alternative donors and analyzed the risk factors for PRES. Overall, 31 children developed calcineurin inhibitor-related PRES (11%), including 30 patients with seizures and 1 patient without seizures...
July 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28588699/irradiation-of-peripheral-blood-mononuclear-cells-with-7-5-gy-x-rays-prior-to-donor-lymphocyte-infusion-inhibits-proliferation-while-preserving-cytotoxicity-and-improves-the-effectiveness-of-hsct-in-patients-with-hematological-malignancies
#18
Yong-Qiu Wei, Xi-Nan Cen, Hui-Hui Liu, Yu-Hua Sun, Yong-Jin Shi, Wei Liu, Yu-Jun Dong, Han-Yun Ren
The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28584210/atopic-dermatitis-like-graft-versus-host-disease-and-lichen-planus-like-graft-versus-host-disease-alterations-in-skin-barrier-function-and-related-molecules
#19
Kun Li, Zhang-Lei Mu, Xue Chen, Guang-Dong Wen, Yan Zhao, Jian-Zhong Zhang
BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms. METHODS: Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28561378/epidemiology-of-bloodstream-infections-after-myeloablative-and-non-myeloablative-allogeneic-hematopoietic-stem-cell-transplantation-a-single-center-cohort-study
#20
Lars I Gjaerde, Claus Moser, Henrik Sengeløv
BACKGROUND: Patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) often develop bloodstream infections (BSI). We aimed to describe the etiologies and antibiotic resistance patterns of BSI after allo-HSCT, and, as knowledge about the impact of conditioning regimen is limited, we looked at the incidence, timing, risk factors, and mortality of BSI separately for myeloablative (MA)- and non-myeloablative (NMA)-conditioned patients. METHODS: All 460 patients (207 MA- and 253 NMA-conditioned) who underwent their first allo-HSCT at our center from 2008 to 2013 were included in a historical cohort...
May 31, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
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