Correspondence

Alemtuzumab for Refractory Celiac Disease in a Patient at Risk for Enteropathy-Associated T-Cell Lymphoma

N Engl J Med 2006; 354:2514-2515June 8, 2006

Article

To the Editor:

A 56-year-old woman had a two-year history of refractory celiac disease for which she had taken prednisone (20 mg per day) for the previous six months, during which time her condition had worsened despite a gluten-free diet. Duodenal biopsy showed severe atrophy with crypt hyperplasia and increased intraepithelial lymphocyte counts. On immunohistochemical analysis, the cytoplasm was positive for CD3 and negative for CD4 and CD8 (Figure 1Figure 1Duodenal-Biopsy Specimens before and after Alemtuzumab Therapy.). Flow-cytometric analysis of intraepithelial lymphocytes showed that more than 50 percent of the cells expressed T-cell receptor γδ (TCRγδ). In addition, we identified a second aberrant population of intraepithelial lymphocytes, which stained negative for surface CD3, CD16/56, and CD19. Polymerase-chain-reaction analysis of DNA extracted from duodenal mucosa and peripheral blood showed oligoclonality of TCRγδ. Computed tomography of the abdomen, an intestinal barium study, colonoscopy, and enteroscopy did not show any evidence of enteropathy-associated T-cell lymphoma.

After a discussion of the risks and benefits, the patient decided to undergo immunotherapy with alemtuzumab, an anti-CD52 monoclonal antibody. Alemtuzumab was administered according to the conventional therapeutic schedule used in cases of chronic lymphocytic leukemia that is resistant to alkylating agents (30 mg two times per week for 12 consecutive weeks). Cytomegalovirus disease developed after the first month of therapy and was treated successfully with ganciclovir.

After nine months of treatment, the patient remained asymptomatic. Prednisone was withdrawn after eight weeks of alemtuzumab therapy. Duodenal biopsy showed total recovery (Figure 1). Flow-cytometric analysis of the duodenal mucosa confirmed a clear decrease in two lymphocyte populations. Polyclonal TCRγδ rearrangement was found in duodenal mucosa, with residual oligoclonality in peripheral blood.

Patients with refractory celiac disease have an increased risk of enteropathy-associated T-cell lymphoma.1 The risk is especially high in refractory celiac disease type II, in which an aberrant population of intraepithelial lymphocytes and clonal TCRγδ rearrangement develop and spread outside the intestine.2 In small case series, conventional immunosuppressive drugs induced remission in 10 to 50 percent of patients.3

Several monoclonal antibodies have already been approved for hematologic neoplasms, and some others are being studied in clinical trials as biologic therapy for autoimmune diseases.4 We chose alemtuzumab for this patient because her mucosal and peripheral intraepithelial lymphocytes expressed CD52 at high levels. Although monoclonal antibodies may have severe side effects, we thought the benefits outweighed the risks in our patient because of the high risk of lymphoma and the lower expected efficacy of conventional treatments. We reasoned that alemtuzumab might be useful to control the aberrant lymphocyte population while the burden of disease was low and before the accumulation of successive genetic errors made eradication more difficult. Although larger studies are needed, the positive response in our patient is an interesting starting point.

Santiago Vivas, M.D.
José María Ruiz de Morales, M.D.
Fernando Ramos, M.D.
Dimas Suárez-Vilela, M.D.
Hospital de León, 24071 León, Spain
svivasa@medynet.com

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Citing Articles (24)

Citing Articles

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   Luis Vaquero, María G. Alvarado, Laura Arias, Sara Calleja, Mercedes Hernando, Cristina Diez-Tascón, Santiago Vivas. (2011) Linfoma intestinal de células T asociado a enteropatía y sin relación con enfermedad celíaca. Gastroenterología y Hepatología
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