Disease management: a systems approach to improving patient outcomes

Approximately 20-30% of patients with non-Hodgkin's lymphoma will be found, after staging, to have stage I or II disease (Anderson et al., 1982; Simon et al., 1979). Here, I consider the present state of our knowledge of the appropriate management of those with low or intermediate grade disease and the relevance of recent observations. Much of the literature combines extranodal with nodal lymphoma, particularly for intermediate grade disease. This can have a distorting effect as these entities may have different natural histories and our focus here is mainly on nodal disease. The Working Formulation histological classification is used, although most of the older literature uses the Rappaport classification. Low grade non-Hodgkin's lymphoma A number of reports have analysed the natural history and therapy of stage I and II low grade lymphoma (Paryani et al. include the histological subtypes small lymphocytic, follicular small cleaved, follicular mixed and follicular large cell. This latter type should, however, almost certainly be managed as an intermediate grade lymphoma in accordance with its clinical course (Kantarjian et al., 1984). The low grade lymphoma are known to disseminate early, and involvement of widespread nodal sites, the liver, spleen and bone marrow are common. In general, more intensive staging will markedly reduce the proportion of patients who remain in stages I and II. All patients should, as a minimum, have a chest X-ray and either lymphangiogram plus ultrasound or abdominal CT, together with a unilateral bone marrow trephine and aspirate. While staging laparotomy is no longer recommended, it is known that approximately 40% of patients with stage I and II disease after these investigations will be stage III or IV as a result of this technique (Goffinet et al., 1977). Surgery has also revealed the inadequacy of a negative lymphangiogram in predicting the presence of intra-abdominal disease-which is present in a substantial proportion of such cases (Castellino et al., 1983). Techniques such as flow cytometry for kappa/lambda ratios (Smith et al., 1984) or the polymerase chain reaction (Stetler-Stevenson et al., 1988), have recently been used to demonstrate more widespread clinically inapparent disease. However, the clinical significance of such findings is at present uncertain. Once staging is complete, approximately 5-10% of patients will be found to have stage I and 10-15% stage II disease. Low grade lymphoma is very sensitive to radiotherapy and local control using this treatment modality occurs in the vast majority of cases (Fuks et al., …