title: Cladribine therapy in refractory celiac disease with aberrant T cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Abdulbaqi
authors.initials: A
authors.lastname: Al-Toma
authors.forename: Marije S
authors.initials: MS
authors.lastname: Goerres
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Meijer
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wahab
authors.forename: Jo A M
authors.initials: JA
authors.lastname: Kerckhaert
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
mesh_terms: D000368:Aged; D002446:Celiac Disease / Q000188:drug therapy* / Q000503:physiopathology; D017338:Cladribine / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D019675:Genes, T-Cell Receptor gamma / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D017338:Cladribine