HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

Malnutrition is a common finding in patients with liver cirrhosis. Malnutrition has been shown to be associated with increased morbidity and mortality. Its pathogenesis remains unclear but both poor dietary intake and increased energy expenditure have been reported.Spontaneous bacterial peritonitis is an important clinical problem in cirrhotics. It may occur as a consequence of repeated access of bacteria from the intestinal lumen (translocation) to the mesenteric lymph nodes. One of the mechanisms proposed to explain bacterial translocation in cirrhosis includes increased intestinal permeability.The aims of the present study were to evaluate GI symptoms in cirrhotic patients and their possible relation to nutritional status, to assess whether gastric sensorimotor dysfunction or metabolic disturbances are associated with reduced food intake, and to investigate the role of ascites in intestinal permeability in patients with liver cirrhosis.Gastrointestinal symptoms and health-related quality of life (HRQOL) were assessed with the aid of two questionnaires. Gastric sensorimotor function was measured by means of an electronic barostat. Food intake, as assessed with a food diary, was related to fasting and postprandial glucose, insulin, leptin, and ghrelin concentrations. Intestinal permeability was evaluated by a 51 Cr-EDTA permeability test. Cirrhotics were found to have increased severity of GI symptoms compared with reference values from the general population. A relationship between GI symptoms and compromised HRQOL as well as weight loss was observed.Proximal stomach relaxation to a meal was increased in patients with liver cirrhosis as compared with healthy controls but the relation between gastric accommodation and energy intake was found to be disturbed in these patients. Gastric sensitivity to distension was shown to be related to GI symptom severity and to liver cirrhosis severity scores.Patients with liver cirrhosis exhibited higher postprandial insulin and glucose concentrations compared to controls. Cirrhotics had higher fasting leptin that fell significantly postmeal and they showed an attenuated increase of ghrelin before the next expected meal. Altered glucose and hormonal levels in patients with cirrhosis were associated with poor food intake.Only a few patients with cirrhosis had increased intestinal permeability, as assessed by a 51 Cr-EDTA test, which was not influenced to a major extent by ascites. Conclusions: In patients with liver cirrhosis GI symptom severity is high and it is associated with impaired HRQOL and weight loss. Gastric accommodation is not involved in the poor food intake observed in cirrhotics and gastric sensitivity seems to be a relevant factor for GI symptom generation in these patients. Altered postprandial glucose, leptin, and ghrelin levels are correlated to reduced energy intake in this patient group. Increased intestinal permeability is probably of limited importance in the pathophysiology of bacterial infections in patients with liver cirrhosis and ascites.

The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.

Graft-versus-host disease (GVHD) is the primary complication of allogeneic, hemopoietic, stem cell transplantation (HSCT). Murine models suggest that gut toxicity, induced by the intensive chemotherapy preceding hematopoietic stem cell infusion, aggravates systemic GVHD. In HSCT patients gut toxicity correlates with chemotherapy intensity. The present study investigates acute GVHD severity and intestinal toxicity in patients undergoing allogeneic HSCT. In 38 patients intestinal permeability was assessed before and after chemotherapy (on days -1, +4, +7 and +14 as related to the stem cell infusion). Cumulative acute GVHD (days 0-100) and clinical intestinal toxicity (days 0-14) were evaluated in parallel. Patients with mild, acute GVHD (grades 0-I) had better-preserved intestinal barrier function (P=0.04) and less pronounced cumulative clinical intestinal toxicity (P=0.02) compared with patients with more severe acute GVHD (grades II-IV). Gut toxicity predicts acute GVHD severity. Therefore, gut protective strategies may diminish GVHD severity in allogeneic HSCT patients.

SummaryAtypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates.