Cladribine therapy in refractory celiac disease with aberrant T cells.
Clin Gastroenterol Hepatol
; 4(11): 1322-7; quiz 1300, 2006 Nov.
Article
in En
| MEDLINE
| ID: mdl-16979946
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Celiac Disease
/
Lymphoma, T-Cell
/
Cladribine
/
Genes, T-Cell Receptor gamma
/
Immunosuppressive Agents
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Gastroenterol Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2006
Document type:
Article
Affiliation country:
Netherlands