Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience

Abstract

Background: Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenotypically normal and aberrant intraepithelial T-cell population, respectively. RCD I seems to respond well to azathioprine/prednisone therapy. RCD II is usually resistant to any known therapy and transition into enteropathy-associated T-cell lymphoma (EATL) is common. Aim: To provide further insight into RCD and the development of EATL, by reporting on long-term survival and risk of transition of RCD into EATL in a large cohort of patients with complicated coeliac disease. Design and Methods: Retrospective comparison of responses to therapy in four groups of patients with complicated coeliac disease: 43, RCD I; 50, RCD II (total), of whom 26 with RCD II developed EATL after a period of refractoriness to a gluten-free diet (secondary EATL) and 13 were EATL patients without preceding history of complicated coeliac disease (de novo EATL). Results: No coeliac-disease-related mortality was recognised in the RCD I group. The overall 5-year survival in the RCD I group it was 96%; in the RCD II (total) group was 58%; and in the RCD II group after developing EATL it was only 8%. The 2-year survival in the de novo EATL group was 20% versus 15% in secondary EATL group (p = 0.63). Twenty-eight (56%) of the 50 patients with RCD II died, 23 (46%) due to EATL, 4 due to a progressive refractory state with emaciation and 1 from neurocoeliac disease. Conclusion: Remarkably, no patient with RCD I developed RCD II or EATL within the mean follow-up period of 5 years (range 2-15 years). A total of 52% of the RCD II patients developed EATL within 4-6 years after the diagnosis of RCD II. More aggressive and targeted therapies seem necessary in RCD II and EATL.

An unexpected deterrent in diagnosing refractory celiac disease and enteropathy-associated T-cell lymphoma: a gluten-free diet

“…The reported survival rates are less than 10% at 5 years and 10–25% at 2 years [6,11]. The mainstay of therapy for EATL is usually chemotherapy and surgical resection.…”

Autoimmune Disorders and Lymphomas

“…The occurrence of an EATL is the main cause of death in RCD patient. About 50-60% of patients with RCD type II develop an EATL within 5 years (Al-Toma et al, 2007, Di Sabatino & Corazza, 2009, Daum et al, 2003. Despite the strong association between CD and EATL, the majority of lymphomas associated with CD are of different histologies, such as DLBCL and peripheral T cell lymphomas (Catassi et al, 2002, Mearin et al, 2006, Halfdanarson et al, 2010.…”

“…Given the dismal prognosis of patients treated with conventional chemotherapy, some authors assessed feasibility and activity of high-dose chemotherapy supported by autologous stem cell transplantation as upfront treatment of EATL, with conflicting results. Most of these studies are based on small retrospective series of patients with disomogeneous characteristics, and utilizing different conditioning regimens (Al-Toma et al, 2007, Bishton & Haynes, 2007. High-dose chemotherapy with IVE/MTX (ifosfamide, vincristine, etoposide, methotrexate) followed by ASCT has been associated with significantly better outcome in comparison with historical controls treated with conventional anthracycline-based chemotherapy.…”

DNAM-1 Mediates Epithelial Cell-Specific Cytotoxicity of Aberrant Intraepithelial Lymphocyte Lines from Refractory Celiac Disease Type II Patients

“…A small proportion of adult-onset celiac disease (CD) patients develops a refractory state with persisting villous atrophy and an increase of intraepithelial lymphocytes (IELs) despite a gluten-free diet (1). Refractory celiac disease (RCD) can be subdivided into RCD type I and type II (RCD II), distinguished by the respective absence or presence of an aberrant IEL population lacking surface expression of the TCR-CD3 complex (surface TCR-CD3 [sTCR-CD3]) (2).…”

“…The cytokine IL-15 that is upregulated in the lamina propria and on epithelial cells of RCD patients (5,6) is thought to be crucial for the expansion and survival of aberrant IELs and lymphoma cells (7). RCD II and RCD-associated lymphoma have poor 5-y survival rates of 44-58 and ,20%, respectively (1,8).…”