Enteropathy-associated T-cell lymphoma
|Enteropathy-associated T-cell lymphoma|
|Classification and external resources|
Enteropathy-associated T-cell Lymphoma (EATL), also enteropathy-type T-cell lymphoma (ETTL), is a type of T-cell lymphoma that affects the small intestine. It is the most common primary gastrointestinal T-cell lymphoma, arising from the T cells that are found between the cells that line the small intestinal (brush border cells or small intestinal epithelial cells). These cancerous T-cells are a possible consequence of refractory cases of coeliac disease or in chronic, untreated cases in genetically susceptible individuals.
EATL is most frequent in Europe, where it represents 9.4% of all peripheral T cell lymphomas. Association with celiac disease is consistently demonstrated in only 30% of patients. The global incidence of this lymphoma is rare, being about 0.5 to 1 per million.
EATL can be classified as an extranodal peripheral T Cell lymphoma, category it shares with Hepatosplenic T cell lymphoma, and Panniculitic T Cell lymphoma. It can be further classified in type I and II EATL.
Enteropathy associated T-cell lymphoma (EATL) is environmentally induced as a result of the consumption of Triticeae glutens (e.g. wheat gluten). In gluten-sensitive individuals with EATL, 68% are homozygotes of the DQB1 subtype at the HLA-DQB1 locus. (See Coeliac Disease, HLA-DQ, HLA DR3-DQ2) A DQ isoform that appears to be responsible for EATL in the overwhelming number of cases is highly effective at presenting a proteolytically protected region of α2-gliadin to T-cells, constant over-stimulation of T-cell eventually results in neoplastic growth. EATL typically appears after the 4th decade of life, within 3 years of coeliac disease diagnosis or in undiagnosed coeliacs. In treated coeliacs, EATL may be preceded by refractory coeliac disease 1(RCD1) or, prominently, refractory celiac disease 2 (RCD2), in which EATL is a frequent outcome. Refractory coeliac disease is no longer favorably responsive to wheat-gluten abstinence. Beyond the RCD1 stage, many drugs are not effective, and undetected coeliac disease leading to de novo EATL generally has a poor outcome.
The genetic association with celiac disease and HLA loci defines type I EATL. Type II doesn´t show these associations and frequently presents with bulky disease.
Early recognition of coeliac disease, particularly with a focus on DQ2 homozygotes and in affected family members, is the only effective prevention, though bone marrow transplant was suggested as a treatment during early RCD2.
Bone marrow involvement is rare in this disease.
In certain eligible patients, a conditioning regimen of high-dose chemotherapy followed by an autologous stem cell transplant may be used to extend a period of first complete remission. Likewise, a recent study suggests that high dose therapy and autologous stem cell transplantation results in favorable outcomes for elderly patients with Non-Hodgkin's Lymphoma.
According to the Peripheral T cell lymphoma project, median overall survival is 10 months, while median failure free survival is only 6 months. The international prognostic index is not useful in defining prognosis in this entity, but Peripheral Index for T cell lymphoma is. Among the most influential prognostic factors is bulky disease, defined by a tumor mass >5 cm.
Autologous Stem Cell Transplant is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of these patients. One study states that there was a trend for better survival in patients transplanted in first complete or partial remission at 4 years (66% vs 36%; P = .062).
- Isaacson PG (October 1994). "Gastrointestinal lymphoma". Hum. Pathol. 25 (10): 1020–9. doi:10.1016/0046-8177(94)90060-4. PMID 7927306.
- Delabie J et al. (July 2011). "Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project". Blood 118 (148): 148. doi:10.1182/blood-2011-02-335216.
- Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ (2007). "Survival in Refractory Coeliac Disease and Enteropathy associated T cell Lymphoma: Retrospective evaluation of single centre experience". Gut 56 (10): 1373–8. doi:10.1136/gut.2006.114512. PMC 2000250. PMID 17470479.
- Jores RD, Frau F, Cucca F et al. (2007). "HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease". Scand. J. Gastroenterol. 42 (1): 48–53. doi:10.1080/00365520600789859. PMID 17190762.
- Al-Toma A, Goerres MS, Meijer JW et al. (2006). "Cladribine therapy in refractory celiac disease with aberrant T cells". Clin. Gastroenterol. Hepatol. 4 (11): 1322–7; quiz 1300. doi:10.1016/j.cgh.2006.07.007. PMID 16979946.
- Al-Toma A, Goerres MS, Meijer JW, Peña AS, Crusius JB, Mulder CJ (2006). "Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma". Clin. Gastroenterol. Hepatol. 4 (3): 315–9. doi:10.1016/j.cgh.2005.12.011. PMID 16527694.
- Al-Toma A, Verbeek WH, Mulder CJ (2007). "Update on the management of refractory coeliac disease". Journal of gastrointestinal and liver diseases : JGLD 16 (1): 57–63. PMID 17410290.
- Meijer JW, Mulder CJ, Goerres MG, Boot H, Schweizer JJ (2004). "Coeliac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment". Scand. J. Gastroenterol. Suppl. 39 (241): 78–84. doi:10.1080/00855920410014605. PMID 15696854.
- Jantunen, E; Boumendil, A; Finel, H; Luan, J. J.; Johnson, P; Rambaldi, A; Haynes, A; Duchosal, M. A.; Bethge, W; Biron, P; Carlson, K; Craddock, C; Rudin, C; Finke, J; Salles, G; Kroschinsky, F; Sureda, A; Dreger, P; Lymphoma Working Party of the EBMT (2013). "Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: A retrospective study by the EBMT". Blood 121 (13): 2529–32. doi:10.1182/blood-2012-11-466839. PMID 23361910.