Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
J Crohns Colitis. 2011 Dec;5(6):543-9. doi: 10.1016/j.crohns.2011.05.004. Epub 2011 Jun 12.
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.
虽然已经开发出了新的治疗策略来控制克罗恩病，但对于难治性病例的治疗仍无法预防广泛和/或反复的手术。最近，有几例报告称，通过造血干细胞移植（HSCT）成功诱导克罗恩病患者缓解。在此，我们报告了我们在 3 名患者中的长期（4 至 6 年）结果。
3 名患有活动性严重克罗恩病的患者计划接受自体 HSCT。所有患者均对常规治疗（包括抗 TNFα 抗体）不耐受或无效。由于小肠广泛受累，患者拒绝手术或手术被认为不可行。
使用环磷酰胺 4 g/m2 单次输注动员外周血干细胞，第 4 天起皮下注射 G-CSF 5 μg/kg，每日两次，直至白细胞分离。白细胞分离后，通过磁性细胞分选分离 CD34+细胞。在这 3 名患者中的 2 名中，由于产量低或 CD34 选择后恢复不足，需要使用 G-CSF 进行第二轮干细胞动员。在移植前，使用环磷酰胺 50mg/kg/天（4 天）、抗胸腺细胞球蛋白 30mg/kg/天（3 天）和泼尼松 500mg（3 天）进行免疫消融。进行了内镜检查、钡剂小肠肠内造影和 MRI 肠造影。
所有 3 名患者均成功完成了干细胞动员，其中 2 名患者随后进行了 CD34+细胞选择的预处理和自体 HSCT。治疗耐受性良好，毒性可接受。现在，移植后 5 年和 6 年后，这些患者在治疗下处于缓解状态。第 3 名患者在动员后缓解，因此决定不进行预处理和 HSCT 移植。成功怀孕后，她在两年后复发。此后，她一直患有难治性克罗恩病，我们现在正在重新考虑预处理和移植。
自体 HSCT 似乎是安全的，对于患有严重和治疗抵抗性疾病的克罗恩病患者来说是一种替代策略。
