Background: Extranodal marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) is a relatively common type of lymphoma. Owing to its B cell lineage, it appears to be a potential target for treatment with the CD20 antibody rituximab. We present an analysis of our experience with rituximab for treatment of patients with advanced MALT lymphoma. Patients and Methods: A retrospective analysis of patients with histologically verified MALT lymphoma undergoing treatment with rituximab was done. After reassessment of histological samples for the presence of MALT lymphoma, patients were evaluated as regards date of diagnosis, prior therapy for MALT lymphoma, sites of involvement upon treatment with rituximab, clinical response in terms of complete remission (CR), partial response (PR), stable disease (SD) and progressive disease as well as symptomatic response, duration of response and survival. Results: A total of 9 patients with advanced MALT lymphoma undergoing therapy with single-agent rituximab were identified. All patients received treatment at a dose of 375 mg/m2 once weekly ×4. One patient each had relapsed after chemotherapy and radiation, respectively, while none of the other 7 patients had received prior cytotoxic treatment or radiation. Three patients achieved a CR, 2 patients had PR for 6 and 14 months, while the remaining patients had SD between 8 and 18+ months. One patient died of progressive disease in spite of the initiation of chemotherapy and 1 patient succumbed to a cardiovascular event while having been in ongoing PR for 11 months. The other 7 patients are currently alive with disease 10–27 months after initiation of therapy. Follow-up biopsies for histological assessment were available in 5 patients with gastric lymphoma. In 1 patient with SD, however, persistence of CD20-positive cells within lymphoepithelial lesions was noted in spite of almost complete depletion of B lymphocytes from the normal gastric mucosa, suggesting either recirculation of MALT lymphoma cells to these lesions or defining lymphoepithelial lesions as a sanctuary site from rituximab penetration. Conclusion: Rituximab had only moderate activity in terms of inducing objective responses in our unselected and heterogeneous cohort of patients with disseminated MALT lymphoma. Long-term disease stabilization, however, along with a symptomatic benefit was seen in all patients. Our data nevertheless indicate that rituximab might not optimally penetrate into the gastric mucosa in all patients.

Keywords:
Rituximab, CD20, Mucosa-associated lymphoid tissue lymphoma
1.
Pileri S, Milani M, Fraternali-Orcioni G, et al: From the REAL classification to the upcoming WHO scheme: A step towards universal categorization of lymphoma entities? Ann Oncol 1998;9:607–612.
2.
Isaacson PG, Wright DH: Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983;52:1410–1416.
3.
Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, et al: Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 1991;338:1175–1176.
4.
Nakamura S, Yao T, Aoyagi K, et al: Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients. Cancer 1997;79:3–11.
5.
Isaacson PG: Gastric MALT-lymphoma: From concept to cure. Ann Oncol 1999;10:637–645.
6.
Neubauer A, Thiede C, Morgner A, et al: Cure of Helicobacter pylori expression and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst 1997;89:1350–1355.
7.
Raderer M, Isaacson PG: Extranodal lymphoma of mucosa associated lymphoid tissue (MALT)-type: Perspective at the beginning of the 21st century. Expert Rev Anticancer Ther 2001;1:89–101.
8.
Hammel P, Haioun C, Chaumette M, et al: Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. J Clin Oncol 1995;13:2524–2529.
9.
Jäger G, Neumeister P, Brezinschek R, et al: Treatment of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT)–type with cladribine (2CdA): A phase II study. J Clin Oncol 2002;20:3872–3877.
10.
Jaffee ES, Harris NL, Stein H, Vardiman JW: World Health Organization Classification of Tumours. Tumours of Haematopoietic and Lymphoid Tissues. Lyon, IARC Press, 2001.
11.
Harris NL: Mature B-cell neoplasms: Introduction, in Jaffee ES, Harris NL, Stein H, Vardiman JW (eds): World Health Organization Classification of Tumours. Tumours of Haematopoietic and Lymphoid Tissues. Lyon, IARC Press, 2001, pp 121–126.
12.
Maloney DG, Smith B, Rose A: Rituximab: Mechanism of action and resistance. Semin Oncol 2002;29(suppl 2):2–9.
13.
Solal-Céligny P: Increasing treatment options in indolent non-Hodgkin’s lymphoma. Semin Oncol 2002;29(suppl 6):2–6.
14.
Coiffier B, Lepage E, Brière J, et al: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235–242.
15.
Visconti J, Petruska P, Dunphy C, et al: Rituximab in the treatment of gastrointestinal (GI) mucosa-associated lymphoid tissue (MALT) lymphoma (abstract). Blood 1999;94(suppl 1):270b.
16.
Dogan A, Du M, Koulis A, et al: Expression of lymphocyte homing receptors and vascular addressins in low-grade gastric B-cell lymphomas of mucosa associated lymphoid tissue. Am J Pathol 1997;151:1361–1369.
17.
Briskin MJ, Windsor-Hines D, Shyjan AM, et al: Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in the intestinal tract and associated lymphoid tissues. Am J Pathol 1997;151:97–110.
18.
Martinelli G, Peccatori F, Laszlo D, et al: Activity of rituximab in relapsed or refractory low-grade marginal zone lymphoma of MALT type of the stomach (abstract). Ann Oncol 2002;13:130.
19.
Conconi A, Thieblemont C, Martinelli G, et al: IELSG phase II study of rituximab in MALT lymphomas (abstract). Ann Oncol 2002:13:81.
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2004
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