Cladribine therapy in refractory celiac disease with aberrant T cells

被引:84
作者
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.
机构
[1] Vrije Univ Amsterdam Med Ctr, Dept Gastroenterol, NL-1005 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Dept Clin Pathol, NL-1005 MB Amsterdam, Netherlands
[3] Vrije Univ Amsterdam Med Ctr, Dept Microbiol, NL-1005 MB Amsterdam, Netherlands
[4] Rijnstate Hosp, Dept Pathol, Arnhem, Netherlands
[5] Rijnstate Hosp, Dept Gastroenterol, Arnhem, Netherlands
关键词
D O I
10.1016/j.cgh.2006.07.007
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. Methods: 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 alpha beta, in the presence of expression of surface CD103 and intracytoplasmic CD3, Treatment consisted of 2-CDA (0.1 mg/kg/day) intravenously for S days, given in 1-3 courses every 6 months depending on the response. Results: 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. Conclusions: 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.
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页码:1322 / 1327
页数:6
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