From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK
From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
QJM. 2014 Nov;107(11):871-7. doi: 10.1093/qjmed/hcu095. Epub 2014 May 5.
Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn's disease (CD), relapse is frequent, and there is little information regarding long-term outcomes in terms of response to subsequent treatments and complications of ASCT.
Retrospective evaluation of UK patients treated on a compassionate basis from three UK tertiary centres.
We summarize long-term outcomes of six previously unreported patients with severe treatment-resistant CD treated with ASCT according to international guidelines between 2003 and 2009. Median duration of CD before ASCT was 14 (7-22) years. Following stem cell mobilization, patients were treated with high-dose cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (7.5 mg/kg) followed by ASCT.
All patients tolerated ASCT with routine toxicities and no treatment-related mortality and are alive at 50-123 months post-ASCT. Clinical and endoscopic remissions of CD were confirmed at 3 months post-ASCT in five patients, although median time to next treatment for inflammatory disease was 10 months (range: 3-16 months). Subsequently, disease control was achieved with previously ineffective and newer treatments, with surgery performed predominantly for pre-existing fibrotic strictures. Two patients became independent of home total parenteral nutrition (TPN). Reported late complications of ASCT included hypothyroidism and ovarian failure.
Long-term follow-up supports the safety and feasibility of ASCT as a means of achieving short-term control of severe CD whilst potentially re-sensitizing the disease to medical therapy and reducing requirements for surgery and TPN. Given the inevitability of relapse, pre-emptive salvage and/or maintenance treatments post-ASCT should be the focus of future trials.
尽管自体干细胞移植(ASCT)可能在严重的治疗抵抗性克罗恩病(CD)中实现疾病控制,但复发很常见,关于后续治疗反应和 ASCT 并发症的长期结果信息很少。
对英国三家三级中心根据同情原则治疗的 UK 患者进行回顾性评估。
我们总结了根据国际指南,2003 年至 2009 年间,六名以前未报告的患有严重治疗抵抗性 CD 的患者接受 ASCT 的长期结果。ASCT 前 CD 的中位病程为 14(7-22)年。在干细胞动员后,患者接受高剂量环磷酰胺(200mg/kg)和兔抗胸腺细胞球蛋白(7.5mg/kg)治疗,然后进行 ASCT。
所有患者均耐受 ASCT,常规毒性反应轻微,无治疗相关死亡,在 ASCT 后 50-123 个月存活。五名患者在 ASCT 后 3 个月时确认 CD 的临床和内镜缓解,但炎症性疾病的下一次治疗中位时间为 10 个月(范围:3-16 个月)。随后,以前无效和更新的治疗方法控制了疾病,主要通过手术治疗先前存在的纤维化狭窄。两名患者能够独立于家庭全胃肠外营养(TPN)。报告的 ASCT 晚期并发症包括甲状腺功能减退和卵巢功能衰竭。
长期随访支持 ASCT 作为实现严重 CD 短期控制的一种安全且可行的方法,同时可能使疾病对药物治疗重新敏感,并减少手术和 TPN 的需求。鉴于复发的必然性,ASCT 后应抢先进行挽救和/或维持治疗,这应成为未来试验的重点。