This bit of research is fresh off the press. It is a retrospective study of 75 non-gastric low grade MALT lymphomas, the largest such study so far. The study followed patients for 9 years, from 1988 to 1997. The 75 patients were previously untreated. They presented with the following locations: lung, orbital soft tissue, skin, thyroid, lachrymal gland, conjunctiva, salivary gland, breast, eyelid, larynx, bone marrow, and trachea. The authors say that the non-gastro sites most often involved by MALT lymphomas are the lung and orbital soft tissue, based on this study.
The researchers note that this disease remains localized to the primary site for long periods of time, and remark on its paradoxical nature -- it rarely arises in places where MALT normally occurs (such as tonsils or Peyer's patches), but instead arises in MALT that has been acquired as a result of some pre-existing condition. The conditions particularly identified were H. pylori infection in the stomach, follicular bronchiectasis of the lung, autoimmune diseases in the salivary and thyroid glands, and reactive or inflammatory lesions of the orbit. They also remark on the correlation between hepatitis C virus infection and extranodal MALT lymphomas. They stress the good prognosis of MALT extranodal lymphomas compared to other extra-nodal lymphomas.
Details on the patients: 35 males and 40 females, median age at dx was 58 (range 27 to 91 years), 63% had limited early stage disease, and 37% had advanced stage disease. 13% had bone marrow involvement. 11% were hepatitis C positive.
The patients were treated by surgery, local radiation, chemo (single or multiple agents), and local intralesional adminstration of interferon alpha. Overall CR rates were 79%, and response rates were 100%. Limited disease patients got 87% CR and 13% PR. Of the advanced disease patients, 64% got a CR and 36% a PR. 88% are still in CR (range of follow up 8 months to 10 and a half years). Some of the relapsed patients got second CRs (3 out of 10). All patients except 2 are alive, and the 2 died of causes other than the lymphoma or its treatment. Estimated relapse rate at 5 years is 30%, and estimated overall survival at 5 years is 95%. Advanced patients had only slightly worse relapse rates at 5 years (29% vs 32%).
The study then describes the treatment and results for the various sites. In summation, the authors state that treatments need to be chosen more on the basis of site than on the basis of stage. All recurrences were still low grade MALT lymphoma. Poorer responses were noted among patients with concomitant mucosal and bone marrow involvement who had a CR rate of 34%. Relapses occurred locally, as dissemination to other organs, or in different areas of the same extranodal site.
Chemotherapy alone was used for lung disease, whereas surgical excision and radiotherapy or local interferon were preferred for the orbital soft tissues and conjunctiva. The 5 patients (conjunctival and lacrymal) who were treated with local administration of interferon alone all got CRs and have not relapsed.
The authors mention work being done on homing receptors and questions of the antigenic sensitivity of this lymphoma, but do not discuss ideas for new treatments. They recommend combination therapy (chemo plus rad) in the majority of sites, and local interferon in sites where radiation could cause unpleasant or dangerous after-effects, and chemo alone for the lung. In terms of duration of response, the thyroid and lacrymal glands did the best, and skin did more poorly.
This study points very clearly, more clearly than I have seen anywhere so far, the underlying infectious or inflammatory processes that lead to lymphoma. It does not discuss the obvious: a recommendation to oncologists to aim for the elimination of such disorders where possible, before other treatments are tried. Such a strategy could lead to "spontaneous regressions," as has been demonstrated with H. pylori in gastric and a few other MALT lymphomas. In addition, would the elimination of hepatitis C result in the regression of lymphoma? Is it possible to eliminate it? (A cursory look at some hepatitis C resources reveal that interferon treatment is used for this disease... either alpha, or other, newer version of it. Some treatments add an antiviral medication as well.)
The other amazing finding is the pronounced and lasting response to local interferon (3 MU three times per week, for 4-6 weeks). Is it possible that this lymphoma type is uniquely responsive to interferon? It seems that this treatment would make sense in other sites, particularly in skin as they note a poor result from surgery (with or without radiation).
Compiled by Vera Bradova © 1999-2001
Updated 3-6-2001