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Gastrointestinal graft vs host

Pam M Ku, Jennifer L Waller, Claude Sportès, Amber B Clemmons
PURPOSE: Hematopoietic cell transplant (HCT) recipients often require intravenous (IV) magnesium repletion due to poor dietary intake, gastrointestinal loss, and use of concomitant magnesium wasting medications. Prolonging the IV magnesium infusion rate has been postulated to reduce renal clearance and improve retention; however, limited evidence supports this hypothesis. METHODS: We reviewed autologous and allogeneic HCT recipients (n = 82) who received IV magnesium at our institution between 2014 and 2016: 41 patients received IV magnesium at a prolonged rate of 0...
March 5, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Ashleigh Scott, Siok-Keen Tey, Jason Butler, Glen A Kennedy
BACKGROUND / AIM: Acute gastrointestinal graft versus host disease (GI-GVHD) following haematopoietic progenitor cell transplantation (HPCT) is a common and life-threatening complication. Endoscopic biopsy of the gastrointestinal tract is required for diagnosis. However, clear evidence to optimise this diagnostic approach is lacking, leading to variation in diagnostic sensitivity between institutions. We aimed to assess the clinical, endoscopic and histological findings of endoscopies performed for suspected acute GI-GVHD at our institution to better define the optimal use of this strategy...
February 1, 2018: Biology of Blood and Marrow Transplantation
Christina Orasch, Dominik Mertz, Jorge Garbino, Christian van Delden, Stephane Emonet, Jacques Schrenzel, Stefan Zimmerli, Lauro Damonti, Konrad Mühlethaler, Alexander Imhof, Christian Ruef, Jan Fehr, Reinhard Zbinden, Katia Boggian, Thomas Bruderer, Ursula Flückiger, Anna Conen, Nina Khanna, Reno Frei, Thomas Bregenzer, Frédéric Lamoth, Véronique Erard, Pierre-Yves Bochud, Thierry Calandra, Jacques Bille, Oscar Marchetti
OBJECTIVES: Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics. METHODS: 3-year prospective study in 567 consecutive candidemias. Species identification and susceptibility testing (CLSI) in reference laboratory. Data analysis according to STROBE criteria. RESULTS: 43/576 (8%) BTC were studied: 37/43 (86%) on fluconazole (28 prophylaxis, median 200mg/day)...
January 26, 2018: Journal of Infection
Thomas Hueso, Jordan Gauthier, Marie Joncquel Chevalier-Curt, Leonardo Magro, Valerie Coiteux, Remy Dulery, Benjamin Carpentier, Julien Labreuche, Gandhi Damaj, Ibrahim Yakoub-Agha, David Seguy
BACKGROUND & AIMS: The gastrointestinal form of acute graft vs host disease increases morbidity and mortality following allogeneic hematopoietic cell transplantation. Plasma levels of citrulline, a non-proteinogenic amino acid, indicate functional enterocyte mass. We measured citrulline in patients before allogeneic hematopoietic cell transplantation and investigated its association with incidence and severity of gastrointestinal graft vs host disease. METHODS: We performed a retrospective study with 191 patients (69 women, 122 men; median age of 52 years) who underwent allogeneic hematopoietic cell transplantation for hematological malignancies at a tertiary center of France from January 2013 through April 2015...
December 16, 2017: Clinical Gastroenterology and Hepatology
Geoffrey Talmon, Tristan Manasek, Ross Miller, David Muirhead, Audrey Lazenby
Objectives: To differentiate apoptotic crypt abscesses (ACAs) from neutrophilic crypt abscesses (NCAs). Methods: Cases with crypt abscesses were classified as containing ACAs, NCAs, or mixed crypt abscesses (MCAs) by H&E staining. Sections were stained with cleaved caspase 3 and myeloperoxidase and recategorized. Results: Fifty-nine cases were reviewed: inflammatory bowel disease (IBD; n = 33), acute cellular rejection (n = 5), graft vs host disease (GVHD; n = 14), cytomegalovirus (n = 5), and drug reaction (n = 2)...
November 20, 2017: American Journal of Clinical Pathology
A M Boyd, A J Perissinotti, J L Nagel, D G Frame, B L Marini
Purpose Allogeneic hematopoietic cell transplant recipients undergo myelosuppressive chemotherapy to allow engraftment of stem cells and are at particularly high risk for bacterial infections and adverse outcomes. Patients undergoing hematopoietic cell transplant are at increased risk for healthcare-associated infections, including infections with multidrug-resistant pathogens. Cefepime is a commonly prescribed antibiotic for empiric therapy in hematopoietic cell transplant patients, but there is minimal data describing cefepime resistance rates, risk factors for resistance, and clinical outcomes associated with cefepime-resistant infections...
January 1, 2017: Journal of Oncology Pharmacy Practice
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...
October 2017: Inflammation
Dana T Lounder, Pooja Khandelwal, Christopher E Dandoy, Sonata Jodele, Michael S Grimley, Gregory Wallace, Adam Lane, Cynthia Taggart, Ashley C Teusink-Cross, Kelly E 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 the risk of graft-versus-host disease (GVHD) through reduced gastrointestinal (GI) 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...
May 18, 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
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