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Graft versus host

X Chen, J L Wei, Y Huang, E L Jiang, Q L Ma, W H Zhai, Y He, R L Zhang, D L Yang, J F Yao, G X Zhang, S Z Feng, M Z Han
Objective: To compare eficacy and safety of porcine antihuman lymphocyte immunoglobulin (pALG) and rabbit antithymocyte immunoglobulin (rATG) as a part of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) for severe aplastic anemia (SAA). Methods: The clinical data of 46 SAA patients received AD allo-HSCT from January 2006 to November 2016 were retrospectively analyzed. The cohort of patients were divided into two groups based on rATG or pALG as a part of conditioning regimen to compare implantation rate, transplantation related complications and outcome...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Dmitry Balashov, Alexandra Laberko, Anna Shcherbina, Pavel Trakhtman, Dmitrii Abramov, Elena Gutovskaya, Svetlana Kozlovskaya, Larisa Shelikhova, Galina Novichkova, Michael Maschan, Alexander Rumiantsev, Alexei Maschan
Our initial experience of hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD; n=12) or a haploidentical related donor (n=6) with TCRαβ+/CD19+ graft depletion for Wiskott-Aldrich syndrome (WAS) patients (n=18) showed a dramatic decrease in the incidence of graft-versus-host disease (GVHD) and transplant-related mortality, with an increased rate of overall survival (OS) of 88,9%. Unfortunately, the treatment was associated with mixed myeloid donor chimerism and secondary graft dysfunction (severe thrombocytopenia, n=2; graft rejection, n=5)...
March 14, 2018: Biology of Blood and Marrow Transplantation
Fevzi F Yalniz, Mohammad H Murad, Stephanie J Lee, Steven Z Pavletic, Nandita Khera, Nilay D Shah, Shahrukh K Hashmi
Given the increasing incidence of cGVHD and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost effectiveness analysis (CEA) for the frequently utilized agents in SR-cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis (ECP), pomalidomide and methotrexate...
March 14, 2018: Biology of Blood and Marrow Transplantation
Somedeb Ball, Kenneth Nugent
Microparticles (MP) are submicron vesicles released from various cells in response to activation, injury or apoptosis. They contain different structural and functional proteins and RNAs, which contribute to physiological intercellular "crosstalk" and to the pathogenesis of various diseases including cancer. In hematological malignancies, these MPs participate in the initiation and propagation of thrombosis through different pathways. They have a role in the angiogenesis, malignant cell survival and metastasis...
March 2018: American Journal of the Medical Sciences
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
Lotte van der Wagen, Liane Te Boome, Marleen Schiffler, Inger Nijhof, Marieke Schoordijk, Suzanne van Dorp, Marijke van Dijk, Reinier Raymakers, Eefke Petersen, Moniek de Witte, Niels de Jong, Mar Bellido, Brigitte Bär, Ellen Meijer, Jürgen Kuball
Sclerotic chronic graft vs. host disease (cGVHD) still has a large impact on morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We performed the first prospective study to test whether sequential therapy of the anti-CD20 antibody rituximab followed by 6 months treatment with tyrosine kinase inhibitor nilotinib is a favorable treatment strategy for patients with sclerotic cGVHD. Twenty-nine patients were included, 24 were available for analysis. We observed objective responses in 71% of patients (two patients CR, 15 patients PR)...
March 16, 2018: Bone Marrow Transplantation
Myrna R Nahas, Robert J Soiffer, Haesook T Kim, Edwin Alyea, Jon Arnason, Robin Joyce, Joseph H Antin, Vincent Ho, Dina Stroopinsky, Shuli Li, James D Levine, Malgorzata McMasters, Salvia Jain, Ayad Hamdan, Dimitrios Tzachanis, Mary Paty Bryant, Emma Logan, Josie Bazemore, Jeremy Stewart, Amy Joyce, Susan Stephenson, Abigail Washington, Leandra Cole, Athalia Pyzer, Rebecca Karp Leaf, David Avigan, Jacalyn Rosenblatt
Steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains a major cause of morbidity and mortality following allogeneic transplantation. Innovative immunotherapeutic strategies are urgently needed for the treatment of SR-cGVHD. We conducted a phase I clinical trial to evaluate the safety, efficacy, and immune effects of abatacept, a novel immunomodulatory drug that acts as an inhibitor of T cell activation via co-stimulatory blockade, in the treatment of SR-cGVHD. The study followed a 3+3 design with two escalating abatacept doses: 3 mg/kg and 10 mg/kg, with an expansion cohort treated at 10 mg/kg...
March 16, 2018: Blood
Isaac Yaniv, Aviva C Krauss, Eric Beohou, Arnaud Dalissier, Selim Corbacioglu, Marco Zecca, Boris V Afanasyev, Massimo Berger, Miguel Angel Diaz, Krzysztof Kalwak, Petr Sedlacek, Stefania Varotto, Christina Peters, Peter Bader
Outcome data were collected from the EBMT registry on 373 children from 120 centers with relapsed leukemia (214 ALL, 159 AML) who underwent second allogeneic hematopoietic stem cell transplantation (HSCT) between 2004 and 2013. At 2 and 5 years, respectively, overall survival (OS) was 38% and 29%, and leukemia-free survival (LFS) was 30% and 25%. Median follow-up after second HSCT was 36.4 months in the ALL group and 50.2 months in the AML group. In the ALL group, at 2 and 5 years, respectively, OS was 43% and 33%, and LFS, 34% and 31%; corresponding values in the AML group were OS 32% and 24%, LFS 24% and 17%...
March 13, 2018: Biology of Blood and Marrow Transplantation
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
Hannah Major-Monfried, Anne S Renteria, Attaphol Pawarode, Pavan Reddy, Francis Ayuk, Ernst Holler, Yvonne A Efebera, William J Hogan, Matthias Wölfl, Muna Qayed, Elizabeth O Hexner, Kitsada Wudhikarn, Rainer Ordemann, Rachel Young, Jay Shah, Matthew J Hartwell, Mohammed Chaudhry, Mina Aziz, Aaron Etra, Gregory A Yanik, Nicolaus Kröger, Daniela Weber, Yi-Bin Chen, Ryotaro Nakamura, Wolf Rösler, Carrie L Kitko, Andrew C Harris, Michael Pulsipher, Ran Reshef, Steven Kowalyk, George Morales, Ivan Torres, Umut Özbek, James L M Ferrara, John E Levine
Acute graft versus host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after one week of therapy often guides further treatment decisions, but long term outcomes vary widely between centers and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken after one week of systemic treatment for GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into test (n=236) and two validation cohorts separated in time (n = 142 and 129, respectively)...
March 15, 2018: Blood
Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Boris Afanasyev, Jan J Cornelissen, Ahmet Elmaagacli, Maija Itälä-Remes, Didier Blaise, Ellen Meijer, Yener Koc, Noel Milpied, Harry C Schouten, Nicolaus Kroeger, Mohamad Mohty, Arnon Nagler
BACKGROUND: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis...
March 15, 2018: Journal of Hematology & Oncology
Lisa M Sharkey, Sarah Peacock, Neil K Russell, Stephen J Middleton, Andrew J Butler
Graft versus host disease (GVHD) following transplantation of an intestine-containing graft occurs more frequently than with other solid organ transplants and is known to have a poor outcome. The presentation differs from other solid organ transplants, as the gastrointestinal tract is not involved following intestinal transplant. Diagnosis is based on clinical symptoms arising due to native tissue damage and the detection of donor T lymphocytes in circulating blood (T cell chimerism). The ideal treatment strategy has not been defined, with advocates for both increased or decreased immunosuppression...
March 15, 2018: Clinical Transplantation
Kotoe Iesato, Tsukasa Hori, Yuko Yoto, Masaki Yamamoto, Natsuko Inazawa, Kenichi Kamo, Hiroshi Ikeda, Satoshi Iyama, Naoki Hatakeyama, Akihiro Iguchi, Junichi Sugita, Ryoji Kobayashi, Nobuhiro Suzuki, Hiroyuki Tsutsumi
BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently experience HHV-6 reactivation typically during early phase following HSCT. However, the long-term clinical complications and prognosis among such patients remain unclear. METHODS: Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6 weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation...
March 14, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
Ines Bojanic, Marinka Mravak Stipetic, Drazen Pulanic, Lana Desnica, Sanja Mazic, Branka Golubic Cepulic, Ranka Serventi Seiwerth, Radovan Vrhovac, Damir Nemet, Steven Z Pavletic
BACKGROUND: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD. STUDY DESIGN AND METHODS: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system...
March 14, 2018: Transfusion
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
Antonella Mancusi, Sara Piccinelli, Andrea Velardi, Antonio Pierini
FoxP3+ regulatory T cells (Tregs) are a subset of CD4+ T cells that can suppress proliferation and effector functions of T cells, B cells, NK cells, and antigen-presenting cells. Treg deficiency causes dramatic immunologic disease in both animal models and humans. As they are capable to suppress the function and the proliferation of conventional CD4+ and CD8+ T cells, Treg-based cell therapies are under evaluation for the treatment of various autoimmune diseases and are currently employed to prevent graft-versus-host disease (GvHD) in clinical trials of hematopoietic stem cell transplantation...
2018: Frontiers in Immunology
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
Arti Nanda, Maitham A A Husain, Waleed Al-Herz, Adla Almekaimi, Humoud Al-Sabah, Mohammad Al-Otaibi
BACKGROUND/OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for many life-threatening disorders in children. Chronic graft-versus-host disease (cGVHD) is a significant complication of HSCT, and its treatment is challenging. Skin is the most common organ affected in cGVHD, with protean manifestations posing a challenge in diagnosis and management. The objective was to have a better understanding of the spectrum of chronic cutaneous GVHD (cc-GVHD) in children...
March 14, 2018: Pediatric Dermatology
T Wang, M Remberger, U Axdorph Nygell, M Sundin, A Björklund, J Mattsson, M Uhlin, E Watz
BACKGROUND: The composition of the graft used for allogeneic hematopoietic stem cell transplantation (HSCT) is important for the treatment outcome. Different apheresis devices may yield significant differences in peripheral blood stem cell graft cellular composition. We compared stem cell grafts produced by Cobe Spectra (Cobe) and Spectra Optia (Optia) with use of the mononuclear cell (MNC) protocol, and evaluated clinical outcome parameters such as graft-versus-host disease (GvHD), transplant-related mortality (TRM), relapse, and overall survival...
March 13, 2018: Transfusion
Peter van Balen, Boris van der Zouwen, Alwine B Kruisselbrink, Matthijs Eefting, Karoly Szuhai, Ekaterina S Jordanova, J H F Falkenburg, Inge Jedema
Introduction: Conditioning regimens preceding allogeneic stem cell transplantation (alloSCT) can cause tissue damage and acceleration of the development of graft-versus-host disease (GVHD). T-cell-depleted alloSCT with postponed donor lymphocyte infusion (DLI) may reduce GVHD, because tissue injury can be restored at the time of DLI. In this study, we investigated the presence of tissue injury and inflammation in skin during the period of hematologic recovery and immune reconstitution after alloSCT...
2018: Frontiers in Immunology
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