Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands. Journal of Crohn s and Colitis
(Impact Factor: 6.23).
12/2011; 5(6):543-9. DOI: 10.1016/j.crohns.2011.05.004
Although new therapeutic strategies have been developed to control Crohn's disease, medical treatment for refractory cases is not able to prevent extensive and/or repeat surgery. Recently, several cases have been reported of successful remission induction in Crohn's disease patients by means of hematopoietic stem cell transplantation (HSCT). Here we report our long-term (4 to 6 years) outcome in three patients.
Three patients (two male, one female) with active severe Crohn's disease were planned to undergo autologous HSCT. All patients were intolerant or refractory to conventional therapies, including anti-TNFα antibodies. Patients either refused surgery or surgery was considered not to be a feasible alternative due to the extensive disease involvement of the small intestine.
Peripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4 g/m(2), followed on day 4 by subcutaneous injections with G-CSF 5 μg/kg twice daily until leukapheresis. CD34+ cells were isolated after leukapheresis by magnetic cell sorting. In two of the three patients a second round of stem cell mobilization using G-CSF only was required, either because of low yield or because of insufficient recovery after CD34 selection. Prior to transplantation, immune ablation was achieved using cyclophosphamide 50mg/kg/day (4 days), antithymocyte globulin 30 mg/kg/day (3 days) and prednisolone 500 mg (3 days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed.
All three patients successfully completed stem cell mobilization, and two of them subsequently underwent conditioning and autologous HSCT with CD34+ cell selection. Treatment was well tolerated, with acceptable toxicity. Now, 5 and 6 years post-transplantation, these patients are in remission under treatment. The third patient went into remission after mobilization and therefore she decided not to undergo conditioning and HSCT transplantation. After a successful pregnancy she relapsed two years later. Since then, she suffers from refractory Crohn's disease for which we are now reconsidering conditioning and transplantation.
Autologous HSCT appears to be safe and can be an alternative strategy for Crohn's disease patients with severe and therapy resistant disease.
Available from: Iván Guerra
- "Extracorporeal photopheresis and autologous hematopoietic stem cell transplantation could be alternatives in patients with CD refractory to immunosuppressants and/or anti-TNF-α, although more data are needed.70,71 "
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ABSTRACT: Dovepress 359 R E v i E w open access to scientific and medical research Open Access Full Text Article http://dx.doi.org/10.2147/CEG.S45297 Abstract: Infliximab (IFX) is an effective treatment for inducing and maintaining response in Crohn's disease and ulcerative colitis patients. Some patients present lack of response or loss of response to IFX during maintenance therapy. Empirical management with combination therapy with an immunomodulator, IFX dose escalation, or switching IFX for another antitumor necrosis factor-α drug, mainly adalimumab, is common in clinical practice. Selecting the best choice with the help of serum drug concentrations and trough IFX antibody concentrations could be a very interesting approach. In addition to surgery, a broad spectrum of new drugs has been tested and could expand treatment options in the near future.
Available from: Marcelo Silva
- "Moreover, a plenty of patients may present with deleterious side effects such as nausea, allergy, adrenal impairment and pancreatitis , as a consequence of the current therapies (Rutgeerts et al. 1990; Akobeng and Gardener 2005; Fidder et al. 2009). In view of that, in the last years novel treatment modalities have been tried in patients with severe refractory Crohn's disease and one the most successful approaches has been the use of high-dose immunosuppression protocols, usually involving cyclophosphamide, associated with autologous hematopoietic stem cells transplantation (Burt et al. 2003, 2010; Oyama et al. 2005; Hommes et al. 2011). On the other hand, total body irradiation (TBI) associated with chemotherapy is the first choice in the treatment of some hematological disorders such as follicular lymphoma (Richaud et al. 1998; Chow et al. 2010). "
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ABSTRACT: The main current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated inflammation in the gut. Although these therapies have been successful, they are not curative and it is not possible to predict whether a beneficial response will occur or which patients will be refractory to the treatment. Total body irradiation (TBI) associated with chemotherapy is the first choice in the treatment of some hematological disorders and is an applicable option in the preparation of patients with hematologic diseases for hematopoietic stem cell transplantation. Then, in this study we investigated the association of TBI as immunosuppressive therapy and bone marrow cell (BMC) transplantation as a strategy to induce colitis recovery and immune reconstitution in the TNBS model of intestinal inflammation. TNBS mice treated with TBI associated with BMC transplantation presented elevated gain of weight and an overall better outcome of the disease when compared to those treated only with TBI. In addition, TBI associated or not with BMC reduced the frequency of inflammatory cells in the gut and restored the goblet cell counts. These results were accompanied by a down regulation in the production of inflammatory cytokines in the colon of mice treated with TBI alone or in association with BMC transplantation. The BMC infused were able to repopulate the ablated immune system and accumulate in the site of inflammation. However, although both treatments (TBI or TBI+BMC) were able to reduce gut inflammation, TBI alone was not enough to fully restore mice weight and these animals presented an extremely reduced survival rate when their immune system was not promptly reconstituted with BMC transplantation. Finally, these evidences suggest that the BMC transplantation is an efficient strategy to reduce the harmful effects of TBI in the colitis treatment, suggesting that radiotherapy may be an important immunosuppressive therapy in patients with IBD, by modulating the local inflammatory response.
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