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Chronic graft versus host

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
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
Yongxia Wu, Steven Schutt, Katelyn Paz, Mengmeng Zhang, Ryan P Flynn, David Bastian, M Hanief Sofi, Hung Nguyen, Min Dai, Chen Liu, Ying-Jun Chang, Bruce R Blazar, Xue-Zhong Yu
Chronic graft-versus-host disease (cGVHD) is characterized as autoimmune-like fibrosis and antibody production mediated by pathogenic T-cells and B-cells. MicroRNA (miR)-17-92 influences the survival, differentiation and function of lymphocytes in cancer, infections and autoimmunity. To determine whether miR-17-92 regulates T- and B-cell responses in cGVHD, we generated mice conditionally deficient for miR-17-92 in T-cells, B-cells, or both. Using murine models of allogeneic bone marrow transplantation (allo-BMT), we demonstrate that expression of miR-17-92 in donor T- and B-cells is essential for the induction of both scleroderma and bronchiolitis obliterans in cGVHD...
March 12, 2018: Blood
Manu Jain, Grs Budinger, Borko Jovanovic, Jane Dematte, Sara Duffey, Jayesh Mehta
Pulmonary chronic graft-versus-host disease (p-CGVHD) following allogeneic HSCT is devastating with limited proven treatments. Although sporadically associated with pulmonary toxicity, the proteasome inhibitor bortezomib may be efficacious in p-CGVHD. We sought to establish safety and tolerability of bortezomib in pilot, open-label trial of patients with p-CGVHD. The primary endpoint was adverse events. Efficacy was assessed by comparing FEV1 decline prior to p-CGVHD diagnosis to during the bortezomib treatment period...
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]
Ke Huang, Dun-Hua Zhou, Yang Li, Hong-Gui Xu, Li-Ping Que, Chun Chen, Hong-Man Xue, Hai-Xia Guo, Wen-Jun Weng, Shao-Liang Huang, Jian-Pei Fang
BACKGROUND: The objective of this study was to evaluate the feasibility of a modified conditioning regimen for the treatment of patients with β-thalassaemia major (TM), using unrelated donor peripheral blood stem cell transplantation (UD-PBSCT). METHODS: A modified conditioning regimen based on intravenous busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin was performed in 50 consecutive childhood patients with β-TM and a median age of 4.6 years (range, 2-12 years)...
March 7, 2018: Pediatric Blood & Cancer
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
Ahmad Kheirkhah, Giulia Coco, Vannarut Satitpitakul, Reza Dana
PURPOSE: To evaluate occurrence of subtarsal fibrosis in patients with graft-versus-host disease (GVHD) and to determine its association with ocular surface epitheliopathy. DESIGN: Cross-sectional study. METHODS: We enrolled 40 patients with moderate or severe dry eye disease including 20 patients with chronic ocular GVHD and 20 patients without (as the control group). All patients had a comprehensive ophthalmic assessment including evaluation for subtarsal fibrosis, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer test...
March 2, 2018: American Journal of Ophthalmology
Sharon Elad, Kevin Zinchuk, Shuli Li, Corey Cutler, Jane Liesveld, Nathaniel Treister
BACKGROUND: Chronic graft-versus-host disease (cGVHD) frequently affects the oral mucosa and is generally responsive to topical immunomodulatory therapies. Clinicians may benefit from guidance in choosing the most appropriate therapy with respect to practicality and cost. OBJECTIVE: To assess the economic considerations related to topical immunomodulatory treatments for management of oral mucosal cGVHD and their practical implications. METHOD: Topical treatments used for management of oral cGVHD were obtained from the NIH Consensus document for ancillary and supportive care...
March 1, 2018: Biology of Blood and Marrow Transplantation
Nataliya P Buxbaum, Cemre Robinson, Ninet Sinaii, Alexander Ling, Lauren M Curtis, Steven Z Pavletic, Kristin Baird, Maya B Lodish
Pediatric allogeneic hematopoietic stem cell transplant (AHSCT) recipients with chronic graft-versus-host disease (cGVHD) are at high risk of endocrinopathies, particularly impaired bone mineral density (BMD). However, rates of BMD impairment in pediatric AHSCT recipients with cGVHD have not been well documented. We describe 33 patients with cGVHD that were referred to the NIH for the Natural History of Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease Study (NCT 0092235) and underwent formal BMD assessments via dual-energy X-ray absorptiometry (DEXA)...
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
Steven D Schutt, Yongxia Wu, Chih-Hang Anthony Tang, David Bastian, Hung Nguyen, M Hanief Sofi, MengMeng Zhang, Chen Liu, Kris Helke, Carole Wilson, Lynn M Schnapp, Juan R Del Valle, Chih-Chi Andrew Hu, Xue-Zhong Yu
Hematopoietic stem cell transplantation (HCT) is a curative procedure for hematological malignancies, but chronic graft-versus-host disease (cGVHD) remains a major complication after allogeneic HCT. Because donor B cells are essential for cGVHD development and B cells are sensitive to endoplasmic reticulum (ER) stress, we hypothesized that the IRE-1α/XBP-1 pathway is required for B-cell activation and function and for the development of cGVHD. To test this hypothesis, we used conditional knock-out mice deficient of XBP-1 specifically in B cells...
February 27, 2018: Blood Advances
Stephanie J Lee, Betty K Hamilton, Joseph Pidala, Amin Alousi, Chareeni Kurukulasuriya, Lynn Onstad, Madan Jagasia, George Chen, Corey Cutler, Raewyn Brody, Mukta Arora, Sally Arai, Stefanie Sarantopoulos, Mary E Flowers
In 2014, the National Institutes of Health sponsored the second Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-vs-Host (GVHD). The purpose was to update recommendations about key elements of chronic GVHD research, including definitions for diagnosis, severity scoring, and response measures, based on empirical data published since the first 2005 Consensus Conference. The most significant modifications were to the response assessments, since studies demonstrated difficulty with the first consensus definitions...
February 21, 2018: Biology of Blood and Marrow Transplantation
Koji Kawamura, Hideki Nakasone, Saiko Kurosawa, Kazuki Yoshimura, Yukiko Misaki, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Yuko Ishihara, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Heiwa Kanamori, Takehiko Mori, Satoshi Takahashi, Shuichi Taniguchi, Yoshiko Atsuta, Yoshinobu Kanda
The aim of this study was to develop a new composite endpoint that accurately reflects the long-term success of allogeneic hematopoietic stem cell transplantation (allo-HCT), since the conventional graft-versus-host disease-free, relapse-free survival (GRFS) overestimates the impact of GVHD. First, we validated current GRFS (cGRFS), which recently was proposed as a more accurate endpoint of long-term transplant success. cGRFS was defined as survival without disease relapse/progression or active chronic GVHD at a given time after allo-HCT, calculated using two distinct methods; a linear combination of a Kaplan-Meier estimates approach and a multistate modelling approach...
February 21, 2018: Biology of Blood and Marrow Transplantation
Musa Alzahrani, Maryse Power, Yasser Abou Mourad, Michael Barnett, Raewyn Broady, Donna Forrest, Alina Gerrie, Donna Hogge, Stephen Nantel, David Sanford, Kevin Song, Heather Sutherland, Cynthia Toze, Thomas Nevill, Sujaatha Narayanan
BACKGROUND: The natural history of patients with myelodysplastic syndromes (MDS) is variable. The revised international prognostic score (IPSS-R) is commonly used in practice to predict outcome in patients with MDS both at diagnosis and pre-transplant. However the effect of change in IPSS-R pre-allogeneic stem cell transplant with chemotherapy or hypomethylating agents on post-transplant outcomes is currently unknown. AIM: We assessed if improvement in IPSS-R prognostic score pre HSCT would result in improvement in clinical outcomes post-transplant...
February 20, 2018: Biology of Blood and Marrow Transplantation
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