Aggressive lymphoma

Abstract: Aggressive lymphoma is a rapidly growing tumour of lymphocyte origin, potentially curable with chemotherapy. In a trial by the Nordic Lymphoma Group, 405 patients with aggressive lymphoma were included, and randomised to receive either the standard chemotherapy regimen, CHOP, or a weekly multidrug regimen, MACOP-B. In this trial, MACOP-B was not superior in terms of response, failure-free or overall survival, but was associated with more non-haematological toxicity and with more pronounced negative effects on health-related quality of life (HRQOL). In this study, we were able to validate the prognostic impact of the International Prognostic Index (IPI). In 92 patients, assessment of HRQOL was performed before, during, and after chemotherapy. In this population, chemotherapy was associated with relatively little negative impact on HRQOL, compared to a reference population. In a multivariate analysis of prognostic factors, pre-treatment global quality was identified as an independent prognostic factor. In 259 patients, immunohistochemical analysis of Ki-67, BCL2, p53 and P-glycoprotein was performed. In a multivariate model, high BCL2 expression, high p53 expression and both very high and low Ki-67 expression were associated with poor prognosis, and were shown to provide additional prognostic information to the IPI. Assessment of BCL2 is proposed to be included as a routine procedure in patients with aggressive lymphoma. In 32 patients with diffuse large B-cell lymphoma (DLBL), frozen lymphoma tissue was available, enabling assessment of BCL6 rearrangement with Southern blot. BCL6 rearrangement was detected in six of 50 patients (12%) and among these, a trend towards superior overall and failure-free survival was noted. In a consecutive series of 81 patients with cytogenetically analysed DLBL, the prognostic impact of cytogenetic aberrations of previously proposed prognostic importance, was analysed. In univariate analysis, der(1q)(21-23), was associated with inferior overall survival. Among patients receiving anthracyclin-based chemotherapy, der(1q)(21-23) remained an adverse prognostic factor in a multivariate analysis, stratified for IPI. The implications of these results in relation to current findings in prognostication and treatment of patients with aggressive lymphoma is discussed.