Department of Haematology.
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Ann Oncol. 2010 Aug;21(8):1706-1711. doi: 10.1093/annonc/mdp596. Epub 2010 Jan 20.
Currently, objective tests are lacking that enable the extent and duration of intestinal mucosal damage induced by myeloablative chemotherapy to be determined. To address this problem, we explored a citrulline-based assessment score as this amino acid is a simple quantitative marker of intestinal failure.
From March 2004 to June 2007, citrulline concentrations were determined at baseline and at least once weekly after the start of myeloablative chemotherapy until 30 days thereafter among 94 allogeneic or autologous haematopoietic stem-cell transplant recipients. The patients were divided into three groups according to the regimen they received: (i) carmustine, etoposide, cytarabine and melphalan/high-dose melphalan, (ii) cyclophosphamide and total body irradiation +/- antithymocyte globulin and (iii) idarubicin-containing regimens. Intestinal mucosal damage was described either by level of citrulline on each day, on the basis of different thresholds of citrulline indicating the severity of villous atrophy, or by area under the curve using reciprocal value of 10/citrulline.
Regimens that incorporated idarubicin induced the most severe intestinal toxicity. Scores based on the level of citrulline, using severity thresholds, and on the area under the reciprocal curve are able to discriminate between the damage induced by different high-dose chemotherapy regimens.
A citrulline-based assessment score appears objective, validated, reproducible, reliable, specific and sensitive making it a suitable first choice for measuring and monitoring intestinal mucositis.
目前,缺乏能够确定骨髓清除化疗引起的肠黏膜损伤程度和持续时间的客观检测方法。为了解决这个问题,我们探索了一种基于瓜氨酸的评估评分方法,因为这种氨基酸是肠衰竭的简单定量标志物。
2004 年 3 月至 2007 年 6 月,94 例异基因或自体造血干细胞移植受者在开始骨髓清除化疗后至少每周测定一次瓜氨酸浓度,直至 30 天后。根据患者接受的方案将其分为三组:(i)卡莫司汀、依托泊苷、阿糖胞苷和马法兰/大剂量马法兰,(ii)环磷酰胺和全身照射 +/-抗胸腺细胞球蛋白,以及(iii)含蒽环类药物的方案。通过每天的瓜氨酸水平、不同瓜氨酸阈值表示绒毛萎缩严重程度的基础上以及通过倒数 10/瓜氨酸的曲线下面积来描述肠黏膜损伤。
含蒽环类药物的方案诱导了最严重的肠道毒性。基于瓜氨酸水平、严重程度阈值以及倒数曲线下面积的评分能够区分不同大剂量化疗方案引起的损伤。
基于瓜氨酸的评估评分方法具有客观性、有效性、可重复性、可靠性、特异性和敏感性,是测量和监测肠黏膜炎的首选方法。