Leung Y, Geddes M, Storek J, Panaccione R, Beck P L
Department of Medicine, University of Calgary, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
World J Gastroenterol. 2006 Nov 7;12(41):6665-73. doi: 10.3748/wjg.v12.i41.6665.
To review all studies in the literature that have assessed Hematopoietic cell transplantation (HCT) and Crohn's disease (CD) with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD.
An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn's disease and inflammatory bowel disease.
We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor (that had no signs or symptoms of CD) and the recipient had several haplotype mismatches in HLA class III genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications.
Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.
回顾文献中所有评估造血细胞移植(HCT)与克罗恩病(CD)的研究,最终目的是确定这对CD患者而言是否为可行的治疗选择。次要目的是回顾上述文献,并确定这些研究是否能进一步阐明CD发病机制中涉及的机制。
使用关键词“骨髓移植”“干细胞”“造血细胞”“克罗恩病”和“炎症性肠病”,对1970年至2005年的所有文章进行广泛的医学文献数据库(Medline)检索。
我们发现1例患者在接受来自患有CD的同胞的异基因HCT后发生了CD。还发现了遗传易感性转移导致CD发生的证据,有报告称1例患者在异基因HCT后发生了严重的CD。HCT后发现,供者(无CD体征或症状)和受者在IBD3位点的HLA III类基因中有几个单倍型错配,包括与CD相关的NOD2/CARD15多态性。共确定了33例已发表的接受自体或异基因HCT的CD患者病例。在发表时,这33例患者中有29例被认为处于缓解状态。中位随访时间为7年,异基因和自体HCT分别为20个月。对于主要因治疗CD而接受HCT的患者,没有与移植并发症相关的死亡病例。
总体而言,这些初步数据表明,异基因和自体HCT在诱导难治性CD缓解方面可能都是有效的。这支持了血液淋巴细胞在CD中起关键作用的假说,以及免疫系统重置可能是CD管理或治愈的关键方法这一观点。