Non-Hodgkin's lymphomas: immunologic prognostic studies

Non-Hodgkin's lymphomas are malignant lymphoproliferative disorders that originate from B or T-lymphocytes and rarely from NK cells. They represent an extremely heterogeneous group of diseases regarding histologic subtypes, clinical presentations, immunophenotypic profiles, cytogenetic and molecular features and suitable mode of treatment. A clinical indicator of prognosis, the International Prognostic Index, takes into account factors that are mostly linked to patient characteristics (age, performance status) and to disease extension and growth (disease stage, s.lactate dehydrogenase level and extent of extranodal involvement). However, it is clear that differences in clinical features and in treatment responses are a result of the marked genetic, immunophenotypic and molecular heterogeneity that underlie disease aggressiveness and tumour progresssion. We applied IPI (based on pretreatment clinical characteristics) in our group of 136 patients that identified a subgroup of clinical features that remained independently significant in multivariate analyses. In our results IPI turned out to be of prognostic significance for response rate and survival percentages. Based on their number of "poor risk" factors, patients were placed into four IPI risk groups: low (one or no risk factors), low-intermediate (two risk factors), intermediate-high (three risk factors), and high (four or five risk factors) with five years survival rates of 88%; 82%; 18% and 0% respectively. However, one limitation of this prediction strategy is that IPI does not encompass molecular abnormalities of tumour cells, which may play a critical role in determining profoundly different clinical outcomes in patients within the same group as defined by IPI. The aim of this study was to assess the clinical significance and potential prognostic value of the expression of the new immunologic prognostic markers including nuclear proliferating antigen, suppressor and oncogenic proteins, HLA-DR surface antigens, tumour infiltrating T-lymphocytes, lymphocyte homing receptor and angiogenic molecules. Immunohistochemistry was used to examine paraffin-embedded tumour tissues for determining the expression of immunologic prognostic markers. Survival analysis showed that serum-high lactate dehydrogenase level, poor performance status (ECOG 3, 4 and 5), high proliferative activity defined as nuclear Ki67 expression greater than 60% of malignant cells and high tumour invasive potential defined by discontinued or loss of Collagen IV were found as strong predictors of poor survival among these patients. These four prognostic parameters determined the New-PI with three risk groups: good (0-1 risk factors), intermediate (2 risk factors) and poor (3 and more risk factors), with predicted five-years survival rates of 88%, 64% and 0%. The New-PI more accurately predicts the outcome than the standard IPI (p < 0,001 vs. p < 0.0001). Based on a single institution series of 136 patients the IPI has proved to be a useful prognostic tool for NHL patients. Addition of new cellular markers into the standard IPI significantly improves risk stratification in NHL.