Al-Toma Abdulbaqi, Goerres Marije S, Meijer Jos W R, von Blomberg B Mary E, Wahab Peter J, Kerckhaert Jo A M, Mulder Chris J J
Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
Clin Gastroenterol Hepatol. 2006 Nov;4(11):1322-7; quiz 1300. doi: 10.1016/j.cgh.2006.07.007. Epub 2006 Sep 18.
BACKGROUND & AIMS: Refractory celiac disease (RCD) may be subdivided into RCD types I and II with phenotypically normal and aberrant intraepithelial T-cell populations, respectively. In RCD II, transition into enteropathy-associated T-cell lymphoma (EATL) is seen frequently. We have evaluated the effect of cladribine (2-CDA), a purine analogue inducing T-cell depletion, on clinical, histopathologic, and immunologic parameters, as well as the toxicity and side effects in a group of RCD II patients.
Between 2000 and 2005, 17 patients were included (8 men, 9 women). All patients had a clonal rearrangement of the T-cell receptor gamma gene and immunophenotyping showed an aberrant T-cell population lacking surface expression of CD3, CD8, and T-cell receptor alphabeta, in the presence of expression of surface CD103 and intracytoplasmic CD3. Treatment consisted of 2-CDA (0.1 mg/kg/day) intravenously for 5 days, given in 1-3 courses every 6 months depending on the response.
All patients tolerated 2-CDA without serious side effects. Six patients (35.8%) showed a clinical improvement (weight gain, improvement of diarrhea, and hypoalbuminemia). In 10 patients (58.8%) a significant histologic improvement and in 6 patients (35.2%) a significant decrease in aberrant T cells was seen. Seven patients (41.1%) developed EATL and died subsequently. One patient died of progressive refractory state with emaciation.
Treatment with 2-CDA in RCD II is feasible, well tolerated, and can induce clinical and histologic improvement as well as a significant decrease of aberrant T cells in a subgroup of patients, albeit it does not prevent EATL development. However, the earlier reported potential risk of precipitating an overt lymphoma should be taken into consideration.
难治性乳糜泻（RCD）可分为I型和II型，其上皮内T细胞群分别表现为表型正常和异常。在RCD II型中，常可见向肠病相关T细胞淋巴瘤（EATL）的转变。我们评估了嘌呤类似物克拉屈滨（2-CDA）诱导T细胞耗竭对一组RCD II型患者的临床、组织病理学和免疫学参数以及毒性和副作用的影响。
2000年至2005年期间，纳入了17例患者（8例男性，9例女性）。所有患者均有T细胞受体γ基因的克隆重排，免疫表型分析显示存在异常T细胞群，其缺乏CD3、CD8和T细胞受体αβ的表面表达，但有表面CD103和胞质内CD3的表达。治疗方案为静脉注射2-CDA（0.1mg/kg/天），持续5天，根据反应情况每6个月给予1 - 3个疗程。
所有患者均耐受2-CDA，无严重副作用。6例患者（35.8%）临床症状改善（体重增加、腹泻改善、低白蛋白血症改善）。10例患者（58.8%）组织学有显著改善，6例患者（35.2%）异常T细胞显著减少。7例患者（41.1%）发生EATL并随后死亡。1例患者死于进行性难治状态伴消瘦。
RCD II型患者使用2-CDA治疗是可行的，耐受性良好，可使部分患者临床和组织学改善以及异常T细胞显著减少，尽管不能预防EATL的发生。然而，应考虑到先前报道的引发明显淋巴瘤的潜在风险。
