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The prognostic significance of age was studied in 372 patients with diffuse large B-cell non-Hodgkin's lymphoma, in relation to the prognostic factors of overexpressed BCL2 and p53 oncoprotein. Overexpression of BCL2 and p53 oncoprotein was defined when more than 50% of the tumor cells showed positive staining. The data were analyzed with respect to the age groups < 65 and > or = 65 years of age. There was a trend for BCL2 overexpression to occur significantly more often among patients older than 65 years of age (P = 0.065). Patients with BCL2 overexpression showed significantly inferior disease free survival rate, but only for patients younger than 65 years (log-rank test P = 0.0002), and the overexpression showed also an independent prognostic significance (P < 0.001). With respect to overexpressed p53 a significant difference was reached for complete remission rate (P = 0.01) and 5-year survival rate (log-rank test P = 0.04), again only for the younger age group. When the analyses were repeated for the older patients who had been treated adequately, the same lack of significance was found, both for BCL2 and p53. This study demonstrates that the negative prognostic value of overexpressed BCL2 and p53 protein is not of concern for patients older than 65 years of age. Among elderly patients the International Prognostic Index score seems the predominant risk factor for inferior prognosis.

The Comprehensive Cancer Centre West (CCCW) population based non-Hodgkin's lymphoma (NHL) registry contains information on all newly diagnosed NHL patients living in the region covered by the CCCW. Patients were entered from June 1st 1981 to December 31st 1989. Follow-up is still ongoing, median follow-up is 113 months (1-191 months) for patients alive. In this study, patient and tumor characteristics, data on patterns of care, response and (relative) survival are described. As follicular lymphomas and diffuse large B-cell lymphomas are the most frequently occurring NHL subtypes in the database, a separate analysis is performed to characterize the clinical picture of these disease entities in the CCCW population. Our data illustrate that NHL patients in the general population are substantially older than patients included in trials and hospital based series. Due to older age, treatment is withheld or adapted for a substantial number of patients. The resulting survival and relative survival rates are a reflection of these choices.

It is debated whether non-Hodgkin's lymphomas originating in Waldeyer's ring (WR NHL) behave as NHL originating in lymph nodes or share common features with extranodal lymphomas originating in mucosa associated lymphatic tissue (MALT). We analyzed data from a population based NHL registry on patterns of dissemination at diagnosis, response to treatment, patterns of failure and survival of 77 primary Waldeyer's ring Non-Hodgkin's lymphomas (WR NHL) patents. Data of completely staged patients with diffuse large cell lymphomas (DLCL) originating in WR (n=44) were compared with those of patients retrieved from the same registry with DLCL originating in lymph nodes or stomach (the latter as prototype of a lymphoma originating in MALT). Primary WR NHL had favorable risk scores according to the International Prognostic Index (IPI), and responded well to therapy: a complete response (CR) rate of 74% was observed. Disease free survival (DFS) and overall survival (OS) were poor, however (47% and 31% at 10 years, respectively). The comparison of DLCL originating in WR, lymph nodes and stomach revealed that WR and gastric NHL patients shared a restricted pattern of dissemination at diagnosis, in contrast to patients with DLCL originating in lymph nodes. Although not all patients were completely restaged at relapse, analysis of patterns of failure suggested that the gastro-intestinal tract is a preferential site for recurrences, both for WR and gastric DLCL patients. CR rates of WR, nodal and gastric DLCL patients were 77%, 55% and 55% respectively (P=0.03), OS of the three patient subgroups did not differ (33%, 27% and 37% at 10 years). DFS of WR DLCL patients was similar to nodal DLCL patients but inferior to gastric DLCL patients (47%, 48% and 73% at 10 years respectively, P=0.006). After Cox regression analysis the relative relapse risk for patients with WR DLCL when compared to patients with DLCL originating in lymph nodes was 2.01 (C.I. 0.99-4.01, P=0.05), and 3.46 (C.I. 1.32-9.00, P=0.01) when compared to patients with gastric DLCL. The clinical picture of primary WR NHL emerging from this population based study is in agreement with data form hospital based studies. In the comparison of WR DLCL, nodal DLCL and gastric DLCL, the observed patterns of dissemination suggest similarities between WR DLCL and gastric DLCL. The frequent relapses after CR observed for WR DLCL patients, however, indicate that these lymphomas clinically behave as nodal DLCL, and should be treated accordingly.

Hairy cell leukemia (HCL) is clinically associated with severe T-cell dysfunction. Several new observations have given more insight into the abnormal T-cell responses seen in this disease. T-lymphocytes in the spleen of patients with HCL seem to be abnormally activated. On the other hand, they are non-responsive, possibly as a result of monocytopenia which may lead to inadequate antigen presentation. This, together with the lack of CD28 on T-cells, may cause T-cell dysfunction. Furthermore, there is a very restricted repertoire of the T-cell receptor-beta family, which may also result in non-responsiveness. Otherwise, T-cell clonal excess may be indicative for activated, possibly autoreactive T-cells.

Diagnostic systems for monoclonal gammopathies use bone marrow and X-ray examinations to exclude multiple myeloma (MM). Data from a population-based registry of unselected patients with paraproteinemia indicate that these tests are often done only when MM is suspected. We used 441 randomly selected patients to develop a simple four point "Myeloma Risk Score" based on two readily available laboratory tests. One point was given for paraprotein concentration > or = 10 g/l, one point for IgG and IgA, and two points for IgD and light chains only. A score of 0 or 1 indicated a low risk for MM, with scores of 2 and 3 signifying high risks. Sensitivity, specificity, positive and negative predictive value (PV) for the Myeloma Risk Score in the training sample were 92%, 88%, 79%, and 96% respectively. Extrapolating these results to a larger cohort showed that 90% of patients with a monoclonal gammopathy could be classified correctly as having MM or a non-myeloma condition. The Myeloma Risk Score can identify patients with a paraproteinemia at risk for MM, and who are therefore candidates for bone marrow and X-ray examination.

An increasing amount of literature has been published concerning the interaction of the CD40 antigen and its ligand with regard to normal B cell ontogeny. In this review, an overview of the CD40 antigen and the CD40 ligand is given, focussing on their possible role in B cell malignancies. Data on the expression of the CD40 antigen on various B cell malignancies (acute and chronic leukemias, non-Hodgkin's lymphoma and multiple myeloma) are presented. The recently developed novel culture "CD40 system" is described. This system is a powerful tool used to culture normal B cells, but also most malignant B cells. We demonstrate in addition a more prominent role of the human Fc receptor presenting murine fibroblasts in the "CD40 system", especially in relation to cultured plasma cells. Finally, some important applications of the "CD40 system" are also summarized.