Cassinotti A, Annaloro C, Ardizzone S, Onida F, Della Volpe A, Clerici M, Usardi P, Greco S, Maconi G, Porro G Bianchi, Deliliers G Lambertenghi
Department of Clinical Science, L. Sacco University Hospital, via G.B. Grassi 74, 20157 Milan, Italy.
Gut. 2008 Feb;57(2):211-7. doi: 10.1136/gut.2007.128694. Epub 2007 Sep 25.
Autologous haematopoietic stem cell transplantation (HSCT) with CD34(+) cell selection has recently been used in the treatment of refractory Crohn's disease, showing good safety and promising efficacy. We investigated the safety and efficacy of HSCT with unselected peripheral blood stem cells (PBSCs) in moderate-severe refractory Crohn's disease.
Four patients (three male, one female; age range 26-45 years) with active moderate-severe Crohn's disease (median Crohn's Disease Activity Index (CDAI) 319, range 272-345), refractory or intolerant to multiple drugs including infliximab, were enrolled.
Unselected PBSCs were collected after mobilisation with cyclophosphamide (CTX) 1.5 g/m2 and granulocyte-colony stimulating factor (G-CSF) 10 microg/kg. The conditioning regimen included CTX 50 mg/kg on days -5 to -2 and rabbit anti-thymocyte globulin (ATG) 2.5 mg/kg on days -4 to -2.
Primary endpoints were toxicity and clinical remission (CDAI<150) at 3 months. Secondary endpoints were clinical and endoscopic response at 3 months and toxicity, clinical and endoscopic remission at 12 months.
No improvement or slight deterioration was observed following mobilisation (median CDAI 339, range 258-404). At the third month, the primary endpoint of clinical remission was achieved in all patients, with a median CDAI of 91 (range 56-102), and complete endoscopic remission was achieved in 2/3 patients. After a median follow-up of 16.5 months, 3/4 patients maintained both clinical and endoscopic remission, despite withdrawal of all drugs, and complete fistula closure was observed in all affected patients. No deaths or life-threatening infection occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another and BK virus-related macrohaematuria in another, all rapidly resolved with conservative treatment.
Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn's disease patients.
采用CD34(+)细胞分选的自体造血干细胞移植（HSCT）最近已用于治疗难治性克罗恩病，显示出良好的安全性和有前景的疗效。我们研究了未分选外周血干细胞（PBSC）的HSCT治疗中重度难治性克罗恩病的安全性和疗效。
纳入4例患者（3例男性，1例女性；年龄26 - 45岁），患有活动期的中重度克罗恩病（克罗恩病活动指数（CDAI）中位数为319，范围272 - 345），对包括英夫利昔单抗在内的多种药物难治或不耐受。
用1.5 g/m²环磷酰胺（CTX）和10 μg/kg粒细胞集落刺激因子（G - CSF）动员后收集未分选的PBSC。预处理方案包括在第 - 5至 - 2天给予CTX 50 mg/kg，在第 - 4至 - 2天给予兔抗胸腺细胞球蛋白（ATG）2.5 mg/kg。
主要终点为3个月时的毒性和临床缓解（CDAI<150）。次要终点为3个月时的临床和内镜反应以及12个月时的毒性、临床和内镜缓解。
动员后未观察到改善或轻微恶化（CDAI中位数为339，范围258 - 404）。在第3个月时，所有患者均达到临床缓解的主要终点，CDAI中位数为91（范围56 - 102），2/3的患者实现了完全内镜缓解。中位随访16.5个月后，3/4的患者尽管停用了所有药物，但仍维持临床和内镜缓解，所有受累患者均观察到瘘管完全闭合。未发生死亡或危及生命的感染。意外不良事件包括1例患者动员后出现肛周脓肿，另1例出现胸腔和心包积液，还有1例出现BK病毒相关的肉眼血尿，所有这些经保守治疗后均迅速缓解。
采用未分选PBSC的自体HSCT似乎是安全的，并且可以诱导并维持既往难治性克罗恩病患者的缓解。
