[Low-grade malignant non-Hodgkin lymphomas--current status and trends in therapy]

Low-grade Non-Hodgkin Lymphomas [NHL] comprise a heterogenous group of disorders both in terms of their cellular and histological composition as in terms of their clinical course. The currently mostly applied classification systems, the Working Formulation and the Kiel Classification as well as the recently proposed Revised European American Lymphoma Classification, discriminate between low-, intermediate and high-grade subtypes. Low-grade NHL are characterized by a low to moderate proliferative activity and a long clinical course with median survival times ranging for approximately three years for centrocytic [CC] or mantle cell lymphomas [MCL] to five to eight years for centroblastic centrocytic [CB-CC] or follicular lymphomas [FL]. Recent cytogenetic and molecular biologic analyses indicate that these differences may result from distinct genetic abnormalities such as the translocation t [14; 18] which is frequently observed in FL-NHL and is associated with a bcl 2 overexpression, or the deregulation of the PRAD 1 in MCL-NHL induced by the translocation t [11; 14]. Therapy of low-grade lymphomas depends mainly on the extend of the disease. In the early stages I and II, at which approximately 15-20% of low-grade NHL are diagnosed, an extended field or a total nodal radiotherapy may be applied with curative intention. The treatment of patients with more advanced stages III and IV is controversial. The currently available information justifies a conservative approach by observing the natural course of the disease until therapeutic intervention is required due to the occurrence of B-symptoms, hematopoietic insufficient or lymphoma progression. Intensive chemotherapy seems not to translate into an improved disease-free or overall survival and can, therefore, not be recommended for first-line treatment. The most recent data of the German Low-Grade Lymphoma Study Group indicate, however, that after successful initial cytoreductive therapy maintenance treatment with interferon-alpha prolongs the disease-free interval and possibly also overall survival. New perspectives have arisen from the introduction of novel cytostatic agents such as purine analogues and the development of immunotoxins and antibody conjugated radioisotopes. Most promising at the present time appears the application of myelo-ablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation which may provide a curative approach even for advanced stages of the disease.