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Gastrointestinal graft vs host

Dana T Lounder, Pooja Khandelwal, Christopher Dandoy, Sonata Jodele, Michael Grimley, Gregory Wallace, Adam Lane, Cynthia Taggart, Ashley Teusink-Cross, Kelly Lake, Stella M Davies
Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce risk of graft versus host disease through reduced intestinal permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 post-transplant...
March 9, 2017: Blood
Bertrand Routy, Caroline Letendre, David Enot, Maxime Chénard-Poirier, Vikram Mehraj, Noémie Charbonneau Séguin, Khaled Guenda, Kathia Gagnon, Paul-Louis Woerther, David Ghez, Silvy Lachance
The intestinal microbiota plays a key role in the pathogenesis of acute graft-versus-host disease (aGVHD). High-dose conditioning regimens given prior to allogeneic hematopoietic stem cell transplantation (aHSCT) modulate the composition of gut microbiota and damage the gut epithelial barrier, resulting in increased systemic inflammation. We assessed whether gut decontamination with antibiotics (ATB) prior to aHSCT influenced the frequency of aGVHD and mortality in 500 patients from two Canadian centers between 2005 and 2012...
2017: Oncoimmunology
Matthew J Hartwell, Umut Özbek, Ernst Holler, Anne S Renteria, Hannah Major-Monfried, Pavan Reddy, Mina Aziz, William J Hogan, Francis Ayuk, Yvonne A Efebera, Elizabeth O Hexner, Udomsak Bunworasate, Muna Qayed, Rainer Ordemann, Matthias Wölfl, Stephan Mielke, Attaphol Pawarode, Yi-Bin Chen, Steven Devine, Andrew C Harris, Madan Jagasia, Carrie L Kitko, Mark R Litzow, Nicolaus Kröger, Franco Locatelli, George Morales, Ryotaro Nakamura, Ran Reshef, Wolf Rösler, Daniela Weber, Kitsada Wudhikarn, Gregory A Yanik, John E Levine, James L M Ferrara
BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups...
February 9, 2017: JCI Insight
Richard B Presland
Chronic graft-vs-host disease (cGVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimmune-like condition that most frequently affects the skin, oral mucosa, liver, eyes and gastrointestinal tract. Both clinical and animal studies have shown that multiple T cell subsets including Th1, Th2, Th17, T follicular helper cells and regulatory T-cells play some role in cGVHD development and progression; B cells also play an important role in the disease including the production of antibodies to HY and nuclear antigens that can cause serious tissue damage...
December 24, 2016: World Journal of Transplantation
Enrique Pérez-Cuadrado-Robles, Cristina Castilla-Llorente, Lucille Quénéhervé, Antonio López-Higueras, Enrique Pérez-Cuadrado-Martínez
INTRODUCTION: The gold standard in the diagnosis of gastrointestinal graft-versus-host disease (GVHD) after allogenic hematopoietic stem cell transplantation is conventional endoscopy with histopathological assessment. The role of capsule endoscopy (CE) is uncertain. The aim of the present study was to investigate the accuracy of CE in this setting, comparing the clinical, endoscopic and histological data. METHODS: This was a retrospective single-centre study that included 57 (mean age: 47...
April 2017: European Journal of Gastroenterology & Hepatology
Enrico Maffini, Luisa Giaccone, Moreno Festuccia, Lucia Brunello, Ilaria Buondonno, Dario Ferrero, Mario Boccadoro, Chiara Dellacasa, Alessandro Busca, Domenico Novero, Benedetto Bruno
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is potentially curative in a variety of hematological malignancies. Graft-vs.-host disease (GvHD) remains a life-threatening complication. Standard treatment is high-dose (HD) corticosteroids. Steroid-refractory (SR) GvHD is associated with poor prognosis. At present, second-line treatment is ill-defined and includes a number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD) highlight the relevant role of the host inflammatory response governed by several kinase families, including Janus kinases (JAK)1/2...
August 8, 2016: Journal of Hematology & Oncology
Marcela Salomao, Kathleen Dorritie, Markus Y Mapara, Antonia Sepulveda
OBJECTIVES: Graft-vs-host disease (GVHD) is a donor T-cell-mediated disorder affecting the recipient's skin, gastrointestinal tract, lungs, and liver. It complicates up to 70% of hematopoietic cell transplantation and is associated with high morbidity and mortality rates. METHODS: An extensive review of the literature has been performed to include the most current consensus on the histopathologic diagnosis of gastrointestinal and liver GVHD. RESULTS: In this review, we present an overview of GVHD, with emphasis on the histopathologic evaluation of gastrointestinal and liver specimens, including the most important differential diagnoses and possible pitfalls...
May 2016: American Journal of Clinical Pathology
Adam Gassas, Joerg Krueger, Tal Schechter, Irina Zaidman, Muhammad Asim, Muhammad Ali
Gastrointestinal (GI) endoscopy and biopsy is a common procedure to confirm the diagnosis of acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Its safety and benefits in aGVHD management is unclear. We aimed to review the safety and benefits of GI endoscopy and biopsy for GI-aGVHD management. From January 2000 to December 2009, 450 Children received allo-HSCT at SickKids. Seventy-nine (17.5%) patients underwent GI endoscopy and biopsy for suspicion of GI-aGVHD...
August 2016: Journal of Pediatric Hematology/oncology
John Koreth, Haesook T Kim, Kyle T Jones, Paulina B Lange, Carol G Reynolds, Marie J Chammas, Katherine Dusenbury, Jennifer Whangbo, Sarah Nikiforow, Edwin P Alyea, Philippe Armand, Corey S Cutler, Vincent T Ho, Yi-Bin Chen, David Avigan, Bruce R Blazar, Joseph H Antin, Jerome Ritz, Robert J Soiffer
Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well tolerated, did not exacerbate alloimmunity, augmented Treg in vivo, and was associated with improvement of active cGVHD. In the current phase 2 study, 35 adults with steroid-refractory cGVHD received daily IL-2 (1 × 10(6) IU/m(2)) for 12 weeks. Median time from transplantation and cGVHD onset was 616 days (range, 270-2145 days) and 317 days (range, 28-1880 days), respectively...
July 7, 2016: Blood
Stephen Ip, Vladimir Marquez, David F Schaeffer, Fergal Donnellan
BACKGROUND: Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation that frequently affects the gastrointestinal (GI) tract. The best biopsy sites to establish the diagnosis have not been clearly established. AIMS: To determine the best sites for obtaining biopsies in evaluating GI GVHD. METHODS: All cases of biopsy-proven GI GVHD (GVHD+) were isolated from a pathology database over a 2-year period at a single tertiary center (n = 46)...
August 2016: Digestive Diseases and Sciences
F Malard, B Gaugler, B Lamarthee, M Mohty
Allogeneic stem cell transplantation (allo-SCT) is a curative therapy for different life-threatening malignant and non-malignant hematologic disorders. Acute graft-vs.-host disease (aGVHD) and particularly gastrointestinal aGVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Better understanding of aGVHD pathophysiology is indispensable to identify new therapeutic targets for aGVHD prevention and therapy. Growing amount of data suggest a role for T helper (Th)17 cells in aGVHD pathophysiology...
March 2016: Mucosal Immunology
Mitsutaka Nishimoto, Hideo Koh, Asao Hirose, Mika Nakamae, Takahiko Nakane, Yoshiki Hayashi, Hiroshi Okamura, Takuro Yoshimura, Shiro Koh, Satoru Nanno, Yasuhiro Nakashima, Toru Takeshita, Akira Yamamoto, Yukimasa Sakai, Norifumi Nishida, Toshiyuki Matsuoka, Yukio Miki, Masayuki Hino, Hirohisa Nakamae
There is no established second-line treatment for steroid-resistant acute graft-versus-host disease (GVHD). We prospectively assessed the safety and efficacy of intra-arterial steroid infusions (IASIs) for steroid-resistant acute gastrointestinal (GI) GVHD and compared the outcomes with those of historical controls at our institution. Nineteen consecutive, allogeneic hematopoietic stem cell transplantation subjects aged 31-67 years (median 52) were enrolled between October, 2008, and November, 2012. Acute GVHD was confirmed by biopsy in all cases...
December 2015: Experimental Hematology
Daniel Trabulo, Sara Ferreira, Pedro Lage, Rafaela Lima Rego, Gilda Teixeira, A Dias Pereira
We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures...
August 14, 2015: World Journal of Gastroenterology: WJG
Anya Levinson, Kerice Pinkney, Zhezhen Jin, Monica Bhatia, Andrew L Kung, Marc D Foca, Diane George, James H Garvin, Jean Sosna, Esra Karamehmet, Chalitha Robinson, Prakash Satwani
BACKGROUND: Bacterial septicemia remains the leading cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (AlloHCT). While murine studies have found acute gastrointestinal graft-vs-host disease (aG-GVHD) to be associated with increased incidence of enteric bacterial bloodstream infections (EB-BSI), this association has not been studied in humans. We hypothesized that in patients who developed aG-GVHD, the EB-BSI density after onset of aG-GVHD would be higher than before onset and higher than in patients without acute GVHD (aGVHD)...
August 1, 2015: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Marco Mielcarek, Terrence Furlong, Barry E Storer, Margaret L Green, George B McDonald, Paul A Carpenter, Mary E D Flowers, Rainer Storb, Michael Boeckh, Paul J Martin
We conducted a phase III study to test the hypothesis that initial therapy with "lower dose" prednisone is effective and safe for patients with newly diagnosed acute graft-versus-host disease. We hypothesized that a 50% decrease in the initial dose of prednisone for treatment of acute graft-versus-host disease would suffice to control graft-versus-host disease without increasing the incidence of secondary treatment. Patients with grade IIa manifestations (upper gastrointestinal symptoms, stool volumes <1...
June 2015: Haematologica
Wenjing Xue, Ming Jiang, Meng Tian, Xianlin Duan, Jianhua Qu, Hailong Yuan, Jianli Xu, Bingzhao Wen, Ling Li, Yichun Wang, Ying Liu, Xinyou Wang, Haizhou Cao
OBJECTIVE: To study the clinical features of acute graft-versus-host disease (aGVHD) and its risk factors for the related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation (RHNT-PBSCT). METHODS: From July 2002 to December 2012, 104 patients who underwent the RHNT-PBSCT were enrolled to analyze the incidences, location and its risk factors of aGVHD, compared with those of the 103 patients who received the HLA-matched sibling non T cell-depleted in vitro PBSCT (MSNT-PBSCT) in the same period...
December 2014: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Johanna Sheu, Arturo P Saavedra, Barbara A Degar, Christine N Duncan, Rima Fawaz, Jennifer K Tan, Birgitta A Schmidt, Heung B Kim, Jennifer T Huang
We present a case of a three-yr-old child with a history of multisystem Langerhans cell histiocytosis treated with systemic chemotherapy, who developed progressive liver failure and received an orthotopic split liver transplant while continuing on chemotherapy. One month following transplant, he developed acute graft-vs.-host disease of the skin and gastrointestinal tract. Peripheral blood chimerism studies post-transplant demonstrated an increasing predominance of donor lymphocytes and granulocytes. Shortly after, the patient developed vitiligo, and two yr after transplantation, the patient developed skin manifestations of psoriasis...
March 2015: Pediatric Transplantation
Francisco Igor B Macedo, Janie Faris, Lawrence G Lum, Ali Gabali, Joseph P Uberti, Voravit Ratanatharathorn, Michael T White
Toxic epidermal necrolysis (TEN) is a rare complication after allogeneic hematopoietic stem-cell transplantation and carries high mortality rates. Graft-vs-host disease (GVHD) is also a life-threatening complication, and potentially indistinguishable from TEN because of similar clinical symptoms. However, current therapeutic recommendations differ between these two conditions, thereby posing a diagnostic dilemma. The authors, herein, present a complicated postoperative course after bone marrow transplantation with concurrent gastrointestinal and hepatic GVHD, and extensive epidermolytic disease compatible with both severe cutaneous GVHD and TEN...
November 2014: Journal of Burn Care & Research: Official Publication of the American Burn Association
David Bürgler, Michael Medinger, Jakob Passweg, Arne Fischmann, Christoph Bucher
BACKGROUND: Acute gastrointestinal GvHD (GI-aGvHD) refractory to first-line treatment with systemic corticosteroids is resulting in death in the majority of patients. We prospectively assessed the feasibility and efficacy of regional intra-arterial steroid treatment in adult patients with severe (≥ grade III) GI-aGvHD not responding to first-line treatment. PATIENTS AND METHODS: Patients with more than +++ GI-aGvHD not responding to intravenous methylprednisolone at a dose of 2mg/kg/day were eligible for inclusion...
February 2014: Leukemia Research
Francis Ayuk, Lara Bussmann, Tatjana Zabelina, Ronja Veit, Haefaa Alchalby, Christine Wolschke, Heinrich Lellek, Ulrike Bacher, Axel R Zander, Nicolaus Kröger
In a retrospective single-centre study, we analysed the prognostic impact of factors identifiable at initial diagnosis of acute GVHD (aGVHD). We retrospectively analysed 495 adult patients of whom 308 (62 %) developed acute GVHD (I-IV) and were included in further analysis. Gut aGVHD was diagnosed in 163/308 cases (53 %). Conditioning was myeloablative conditioning (MAC) in 123 (39.9 %) and reduced intensity (RIC) in 185 (60.1 %) patients. Median serum albumin level at diagnosis of aGVHD was 34 g/l, which was used as cut-off for low vs...
May 2014: Annals of Hematology
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