O.J. Visser

Enteropathy associated T-cell lymphoma and its precursor lesions

Enteropathy Associated T-cell Lymphoma (EATL) is an intestinal tumour of intra-epithelial lymphocytes. Based on morphology, immunohistochemistry and genetic profile EATL can be divided into two groups. EATL type I is a large cell lymphoma which is highly associated with Coeliac Disease (CD) and mostly presents with malabsorption, weight loss and CD-related symptoms. EATL type II consists of small to medium-sized cells and presents often with obstruction or perforation of the small bowel. This type of EATL has no known association with CD. When EATL has been diagnosed a thorough diagnostic work-up is needed. This work-up preferably includes video capsule enteroscopy (VCE), double-balloon enteroscopy (DBE), computed tomography (CT) combined with 18F-fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET scan) if possible and magnetic resonance enteroclysis (MRE). Nowadays, most EATL patients are treated with chemotherapy mostly preceded by resection of the tumour and followed by stem cell transplantation. Despite these therapies outcome of EATL remains very poor with a 5-year survival of 8-20%. In order to improve survival prospective multicentre trials, studying new therapies are needed. The combination of chemotherapy, monoclonal antibodies and/or apoptosis inducing small molecules might be a potential treatment for EATL in the (nearby) future.

Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy

Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60–80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising.

Nutritional support in patients with GVHD of the digestive tract: state of the art

An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD-DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B12 and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies.

Feasibility of Intermittent Fish Oil Infusions in Outpatients with Graft-Versus-Host Disease of the Digestive Tract

N-3 polyunsaturated fatty acids from fish oil may have immune-modulating effects in Graft-versus-Host Disease of the digestive tract (GVHD-DT). The objective of this pilot study was to investigate feasibility, safety and effects on fatty acid composition of plasma lipids and white blood cells (WBC), following intermittent fish oil infusion in outpatients with chronic GVHD-DT. Four outpatients received intermittent infusion of a 10% fish oil emulsion (Omegaven) during 4 hours, at day 1 (1.5 mL/kg), 3 (2.25 mL/kg) and 5, 8, 10 and 12 (3 mL/kg). At baseline and consecutive visits, fatty acid composition of plasma triglycerides (TG), plasma phospholipids (PL) and WBC, serum TG concentrations, routine laboratory tests, as well as adverse events were monitored. During the fish oil infusions, serum TG increased, but decreased 2 h after termination of infusion. In 3 patients, the dose of Omegaven® needed to be reduced. EPA was incorporated into plasma PL, plasma TG and WBC as of 2 days after the first infusion; peak levels of EPA were reached at the final infusion, or 2 days after. In conclusion, intermittent fish oil infusions result in incorporation of EPA in plasma and WBC, but can be complicated by a reversible increase in serum triglycerides.