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Acute GVHD

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
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
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
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
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
Olle Ringden, Arjang Baygan, Mats Remberger, Britt Gustafsson, Jacek Winiarski, Bita Khoein, Guido Moll, Lena Klingspor, Magnus Westgren, Behnam Sadeghi
Severe acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta-derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM-MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21)...
March 13, 2018: Stem Cells Translational Medicine
Zain A Bashey, Xu Zhang, Stacey Brown, Katelin Jackson, Lawrence E Morris, H Kent Holland, Asad Bashey, Scott R Solomon, Melhem Solh
Allografting from HLA-haploidentical donors (HID) is being increasingly utilized worldwide for patients lacking a conventional matched donor. However, its efficacy in older patients with AML and MDS is unclear. We analyzed 127 consecutive allografts for AML/MDS patients aged ≥ 60 years at our center to compare outcomes using HID to those of contemporaneous transplants using matched sibling (MRD) or matched unrelated (MUD) donors. Patient characteristics were similar except HID transplants were more likely in non-white patients and were more commonly performed with reduced intensity conditioning and a marrow graft...
March 9, 2018: Bone Marrow Transplantation
Sanda Mrabet, Narjess Ben Aicha, Nihed Abdessayed, Moncef Mokni, Abdellatif Achour
BACKGROUND: Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits. Most of the cases are primary, while only approximately 25% of the cases are secondary to some known diseases. Recently, MN has been considered to be a possible presentation of chronic graft-versus-host disease (GVHD) of the kidney in allogeneic hematopoietic stem cell transplantation (HSCT) patients. In autologous HSCT populations, there have been scarce reports of associated MN, as a result of immune dysregulation leading to systemic autoimmunity and miming chronic GVHD...
March 9, 2018: BMC Nephrology
L J Liang, J Zhou, Y L Zhang, Y W Fu, Y L Zu, F K Yu, Q D Lin, L J Han, Q Wang, B J Fang, X D Wei, Y P Song
To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS). Clinical outcome including hematopoietic reconstitution, transplant-related complications, survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT. Hematopoiesis reconstitution was achieved in all the 9 recipients. Four cases developed acute graft-versus-host disease (GVHD), and 1 with chronic GVHD...
March 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Joni Keto, Tanja Kaartinen, Urpu Salmenniemi, Johanna Castrén, Jukka Partanen, Arno Hänninen, Matti Korhonen, Kaarina Lähteenmäki, Maija Itälä-Remes, Johanna Nystedt
Mesenchymal stromal cells (MSCs) are used as salvage therapy to treat steroid-refractory acute graft-versus-host disease (aGvHD). We studied the immunological response to MSC treatment in 16 aGvHD patients by assessing lymphocyte profiles and three proposed aGvHD serum markers during the MSC treatment. Surprisingly, there were no obvious differences in the lymphocyte profiles between the responders and non-responders. The numbers of T, B, and NK cells were below the normal reference interval in all patients...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Tatsunori Goto, Makoto Murata
Mesenchymal stem cells (MSCs) have received considerable attention in allogeneic hematopoietic cell transplantation because of their abilities to modulate immune responses and promote hematopoiesis. Because MSCs are capable of producing several cytokines and growth factors, they have been widely used in the treatment of graft-versus-host disease (GVHD). A number of clinical trials have demonstrated the safety and efficacy of MSC therapy for acute GVHD. Moreover, in Japan, allogeneic bone marrow-derived MSC product, TEMCELL® , was approved as a regenerative medicine for acute GVHD...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Tor Henrik Anderson Tvedt, Randi Hovland, Galina Tsykunova, Aymen Bushra Ahmed, Tobias Gedde-Dahl, Øystein Bruserud
BACKGROUND: Interleukin 6 (IL-6) is an important regulator of immunity and inflammation in many diseases. Single nucleotide polymorphisms (SNPs) in the IL-6 gene influence outcome after allogeneic stem cell transplantation (ASCT), but the possible importance of SNPs in the IL-6 receptor has not been examined. We therefore investigated whether SNPs in the IL-6R gene influenced biochemical characteristics and clinical outcomes after ASCT. PATIENTS AND METHODS: We investigated the IL-6 promoter variant rs1800975 and the IL-6R SNPs rs4453032, rs2228145, rs4129267, rs4845374, rs4329505, rs4845617, rs12083537, rs4845618, rs6698040 and rs4379670 in a 101 population-based cohort of allotransplant recipients and their family donors...
March 7, 2018: Clinical and Experimental Immunology
Keiji Kurata, Kimikazu Yakushijin, Atsuo Okamura, Motohiro Yamamori, Hiroya Ichikawa, Rina Sakai, Yu Mizutani, Seiji Kakiuchi, Yoshiharu Miyata, Akihito Kitao, Shinichiro Kawamoto, Hiroshi Matsuoka, Tohru Murayama, Hironobu Minami
PURPOSE: Mycophenolate mofetil (MMF) is increasingly used among Japanese patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Because pharmacokinetic data for MMF in the Asian population are limited, we conducted this investigation. METHODS: Intravenous MMF (1000 mg/dose) was administered to 10 patients along with cyclosporine or tacrolimus for 10 days after allo-SCT; it was administered every 8 h in peripheral blood stem cell- and bone marrow-transplanted patients, and every 12 h in cord blood-transplanted patients...
March 6, 2018: Cancer Chemotherapy and Pharmacology
Muhammad B Hammami, Rebecca Talkin, Ahmad M Al-Taee, Martin W Schoen, Sagun D Goyal, Jin-Ping Lai
Multiple myeloma (MM) is the most common indication for autologous hematopoietic stem cell transplantation (HSCT) in North America. Despite occurring in up to 50% of patients undergoing allogeneic HSCT, the incidence of graft-versus-host disease (GVHD) after autologous HSCT is reportedly only 5-20%. Gastrointestinal involvement with graft-versus-host disease (GI GVHD) is a common and serious complication of allogeneic HSCT. GI GVHD after autologous transplant, which is referred to as autologous GVHD (auto-GVHD), has also been described...
February 2018: Gastroenterology Research
Hideki Sano, Kazuhiro Mochizuki, Shogo Kobayashi, Yoshihiro Ohara, Masaki Ito, Tomoko Waragai, Nobuhisa Takahashi, Kazuhiko Ikeda, Hitoshi Ohto, Atsushi Kikuta
We evaluated the efficacy and toxicity of T-cell-replete haploidentical stem cell transplantation (TCR-haploSCT) using low-dose antithymocyte globulin (ATG) in children with refractory/relapsed (R/R) acute leukemia. From October 2009 to April 2016, 39 consecutive patients with R/R acute leukemia who underwent TCR-haploSCT were included. At the time of TCR-haploSCT, 17 patients were in complete remission (CR), but 22 had active disease. Thirty-three patients received a myeloablative regimen and six received a reduced-intensity conditioning regimen...
March 5, 2018: International Journal of Hematology
Alessandra Forcina, Francesca Lorentino, Vincenzo Marasco, Chiara Oltolini, Magda Marcatti, Raffaella Greco, Maria Teresa Lupo-Stanghellini, Matteo Carrabba, Massimo Bernardi, Jacopo Peccatori, Consuelo Corti, Fabio Ciceri
Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred-forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pre-transplant MDR-GNB colonization and evaluated for clinical outcomes. A pre-transplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM) nor infection-related mortality (IRM) compared to non-carriers...
March 1, 2018: Biology of Blood and Marrow Transplantation
Zachariah DeFilipp, Fabian M Troschel, David A Qualls, Shuli Li, Martin W Kuklinski, Maria Kempner, Ephraim Hochberg, Yi-Bin Chen, Areej El-Jawahri, Florian J Fintelmann
Sarcopenia, the loss of muscle mass, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about change in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Cross-sectional area of lean muscle, subcutaneous adipose tissue and visceral adipose tissue were measured on CT at the level of the third lumbar vertebral body prior to HCT, 1-year post-HCT, and 2...
February 26, 2018: Biology of Blood and Marrow Transplantation
Lixin Xu, Zhouyang Liu, Yamei Wu, Xueliang Yang, Yongbin Cao, Xiaohong Li, Bei Yan, Songwei Li, Wanming Da, Xiaoxiong Wu
BACKGROUND: This study not only evaluated the clinical effects of treatment using haploidentical hematopoietic stem cells (haplo-HSCs) combined with human umbilical cord mesenchymal stem cells (UC-MSCs) in patients with severe aplastic anemia (SAA), but also investigated the factors related to graft versus host disease (GVHD). METHODS: Cotransplantation of haplo-HSCs and UC-MSCs was performed in 24 SAA patients. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide, and fludarabine with or without busulfan...
March 1, 2018: European Journal of Medical Research
Shin Mukai, Yoko Ogawa, Yutaka Kawakami, Yukihiko Mashima, Kazuo Tsubota
Graft-versus-host disease (GVHD) is a potentially lethal complication of hematopoietic stem cell transplantation (HSCT). GVHD comprises acute and chronic forms. To date, several approaches to treat acute GVHD or chronic GVHD have been reported. However, there is no literature precedent regarding all-in-one methods to address the 2 GVHD types. Severe inflammation in organs affected by GVHD is highly problematic, and vascular adhesion protein-1 (VAP-1) is known to be detrimentally involved in various inflammatory diseases...
February 28, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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