Cladribine therapy in refractory celiac disease with aberrant T cells

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.

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 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.

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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Celiac Disease / drug therapy*
  • Celiac Disease / physiopathology
  • Cladribine / pharmacology
  • Cladribine / therapeutic use*
  • Disease Progression
  • Female
  • Genes, T-Cell Receptor gamma / immunology*
  • Humans
  • Immunophenotyping
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Depletion
  • Lymphoma, T-Cell / immunology*
  • Lymphoma, T-Cell / prevention & control*
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes / drug effects


  • Immunosuppressive Agents
  • Cladribine