Autologous Haematopoietic Stem Cell Transplantation for Crohn's Disease: A Retrospective Survey of Long-term Outcomes From the European Society for Blood and Marrow Transplantation

Background and Aims: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with severe, treatment-refractory Crohn’s disease [CD]. The evidence base for AHSCT for CD is limited, with one randomised trial [ASTIC] suggesting benefit. The aim of this study was to evaluate safety and efficacy for patients undergoing AHSCT for CD in Europe, outside the ASTIC trial. Methods: We identified 99 patients in the European Society for Blood and Marrow Transplantation [EBMT] registry, who were eligible for inclusion. Transplant and clinical outcomes were obtained for 82 patients from 19 centres in seven countries. Results: Median patient age was 30 years [range 20–65]. Patients had failed or been intolerant to a median of six lines of drug therapy; 61/82 [74%] had had surgery. Following AHSCT, 53/78 [68%] experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months [range 6–174]; 22/82 [27%] required no medical therapy at any point post-AHSCT. In patients who had re-started medical therapy at latest follow-up, 57% [24/42] achieved remission or significant symptomatic improvement with therapies to which they had previously lost response or been non-responsive. Treatment-free survival at 1 year was 54%. On multivariate analysis, perianal disease was associated with adverse treatment-free survival (hazard ratio 2.34, 95% confidence interval [CI] 1.14–4.83, p = 0.02). One patient died due to infectious complications [cytomegalovirus disease] at Day +56. Conclusions: In this multicentre retrospective analysis of European centres, AHSCT was relatively safe and appeared to be effective in controlling otherwise treatment-resistant Crohn’s disease. Further prospective randomised controlled trials against standard of care are warranted

Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study

Background. The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs. Methods. 285 patients were randomly assigned omeprazole 20 mg, amoxycillin 100 mg, and clarithromycin 500 mg, twice daily (n = 142, H pylori eradication treatment), or omeprazole with placebo antibiotics (n = 143, controls) for 1 week. All patients received omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13-labelled urea breath test at 3 months. Findings. The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment and 0.53 (0.44-0.62) on on control treatment (p = 0.80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H pylori status. 66% (58-74) of the eradication group compared with 14% (8-20) of the control group had a final negative H pylori result (p < 0.001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p = 0.006). Interpretation. H pylori eradication in long-term users of NSAIDs with past or current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.Articl

Supplementary Material for: Serum REG3alpha and C-Reactive Protein Levels in Crohn's Disease Patients Undergoing Immunoablation and Autologous Hemopoetic Stem Cell Transplantation in the ASTIC Trial

<b><i>Background:</i></b> REG3α has been recently shown to be a highly accurate biomarker for graft-versus-host-disease (GvHD). Given the unmet need of such biomarkers in Crohn's disease (CD) and the similarities between CD and GvHD, we aimed at investigating the role of serum REG3α as a diagnostic and prognostic biomarker in CD patients undergoing autologous hemopoetic stem cell transplantation (HSCT) in the multicenter Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) trial and to compare it to C-reactive protein (CRP). <b><i>Methods:</i></b> Stored serum samples from the ASTIC trial were analyzed using a commercially available human PAP1 ELISA-kit to measure REG3α levels. CRP was available from prior analysis in the ASTIC trial. These levels were correlated with clinical and endoscopic disease activity as well as overall clinical and endoscopic outcome 1 year after autologous HSCT. <b><i>Results:</i></b> One hundred thirty two serum samples were available for analysis. The mean concentration of REG3α was 101.8 ng/ml (95% CI 22.6-258.3). No significant elevation of REG3α was found among patients with active disease compared to those in remission (106.3 vs. 91.4). Patients with moderate to severe endoscopic disease activity showed substantially, although not significantly elevated REG3α levels compared to those in remission (95.4 vs. 52.4, p = 0.052). Baseline serum REG3α levels of patients without clinical or endoscopic remission 1 year after HSCT were not elevated compared to those in remission (63.1 vs. 66.9, and 68.4 vs. 59.2, respectively). In contrast, CRP was significantly elevated in patients with active disease compared to patients in remission (14.1 vs. 6.0 mg/dl, p = 0.032). In addition, CRP was elevated, although not significantly, in patients with severe endoscopic disease compared to those in endoscopic remission (18.7 vs. 4.1, p = 0.062). Furthermore, baseline CRP was reduced in patients with clinical and endoscopic remission after HSCT compared to those without remission, although not significantly (8.8 vs. 21.4, n.s. and 8.1 vs. 12.4, n.s.). <b><i>Conclusion:</i></b> Given the divergent findings compared to GvHD, we conclude that serum REG3α is not an accurate diagnostic and predictive biomarker in CD patients undergoing HSCT. In contrast, CRP is a valuable biomarker in order to differentiate active disease from remission. However, CRP does not seem to be of prognostic value for HSCT outcome