Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease

Cassinotti, A.; Annaloro, C.; Ardizzone, Sandro; Onida, Francesco; Volpe, A. Della; Clerici, Mario; Usardi, P.; Greco, Salvatore; Maconi, Giovanni; Porro, G. Bianchi; Deliliers, Giorgio Lambertenghi

doi:10.1136/gut.2007.128694

Cited by 153 publications

(96 citation statements)

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“…14,15 The authors report that 91% of patients achieved medication-free remission after 1 year, which lasted up to 5 years in selected patients. A similar rate of remission was observed in six patients transplanted in Milan 8,16 and in smaller series and independent case reports [reviewed in Refs. (9,17,18)].…”

mentioning

confidence: 51%

Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation

Hasselblatt

Drognitz

Potthoff

et al. 2012

Aliment Pharmacol Ther

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mentioning

confidence: 51%

Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation

Hasselblatt

Drognitz

Potthoff

et al. 2012

Aliment Pharmacol Ther

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“…11,30 Therefore, these evidences suggest that SCT could be justified in some patients with IBD, which have already begun to be transplanted in some current trials, 42,43 thus raising the question of whether the cell transplantation or the intense immunosuppression was the critical event for patient recovery. In our study, both therapeutic approaches induced remission of the disease and, although we did not elucidate the exact mechanisms of action of the graft in the treatment of the IBD, we showed that in this model, the infusion of the graft was extremely important to reduce mortality.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Godoi

Cardoso

Ferraz

et al. 2010

Bone Marrow Transplant

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Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4 þ leukocytes in the inflammatory infiltrate on days þ 7 and þ 14 and of CD8 þ cells on day þ 7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that highdose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.

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“…6 There has been considerable interest in case reports that autologous haematopoietic stem cell transplantation (HSCT) can induce sustained disease remission in such patients. [7][8][9][10][11][12][13] The ASTIC trial compared outcome at one year in 23 patients with refractory CD after autologous HSCT to 22 undergoing stem cell mobilisation alone. 14 This was a negative trial and few patients in either arm achieved the ambitious primary endpoint of clinical remission off therapy for 3 months with no endoscopic or radiological evidence of intestinal inflammation.…”

Section: Introductionmentioning

confidence: 99%

Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial

Lindsay

Allez

Clark

et al. 2017

The Lancet Gastroenterology & Hepatology

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BACKGROUND The randomised controlled ASTIC trial showed no benefit of mobilisation and autologous haematopoietic stem-cell transplantation (HSCT) compared with mobilisation followed by conventional therapy using a stringent primary endpoint (steroid-free clinical remission for 3 months with no endoscopic or radiological evidence of intestinal inflammation) in patients with treatment-refractory Crohn's disease. We now assess HSCT in patients enrolled in the ASTIC trial using endpoints that are traditional for clinical trials in Crohn's disease, and identify factors that predict benefit or harm. METHODS Patients who underwent mobilisation and were randomly assigned to conventional therapy in the ASTIC trial were offered HSCT at 1 year and underwent complete assessment for a further year. We report analyses of the combined cohort of patients who underwent HSCT at any time during the ASTIC trial programme. The primary outcome for this analysis was 3-month steroid-free clinical remission at 1 year after HSCT (Crohn's Disease Activity Index [CDAI] <150). We also examined the degree of endoscopic healing at 1 year. Multivariate analysis was performed to identify factors associated with achieving the primary endpoint by using logistic regression, and factors associated with experiencing a serious adverse event using Poisson regression. Participants were not masked to treatment, but the adjudication panel that reviewed radiology and endoscopy was masked to allocation and visits. All patients who underwent HSCT and had data available at baseline and 1-year follow-up were included in the primary and safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00297193. FINDINGS Between June 28, 2007, and Sept 1, 2011, 45 patients were enrolled in the ASTIC trial from 11 European transplant units. 23 patients were randomly assigned to immediate HSCT, and 22 patients were assigned to mobilisation followed by conventional care. After completion of the ASTIC trial, 17 patients from the conventional care group received HSCT. In the combined cohort, data were available for 40 patients at baseline and 38 patients at 1 year after HSCT (one patient died, one withdrew). At 1 year after HSCT, 3-month steroid-free clinical remission was seen in 13 (38%, 95% CI 22-55) of 34 patients with available data for the whole year. Complete endoscopic healting was noted in 19 (50%, 34-66) of 38 patients. On multivariate analyses, factors associated with the primary outcome were short disease duration (odds ratio [OR] 0·64, 95% CI 0·41-0·997 per year; p=0·048) and low baseline CDAI (0·82, 0·74-0·98 per 10 units; p=0·031). 76 serious adverse events occurred in 23 of 40 patients with available data. The most common serious adverse event was infection, most of which were treatment related. Smoking and perianal disease at baseline were independent factors associated with the number of serious adverse events (OR 3·07 [95% CI 1·75-5·38; p=0·0001] for smoking and 3·97 [2·17-7·25; p<0·0001] for perianal disease) on multivariate...

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Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease

Abstract: Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn's disease patients.

Cited by 153 publications

References 50 publications

Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation

Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial

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