Some prognosticc factors for the therapy of patients with Non-Hodgkin's Lymphomas

Abstract

A number of factors influencing the results of therapy and the outcome of disease for patients with non-Hodgkin's lymphomas have been reviewed. Clearly these factors have a restricted prognostic value in a large number of cases, because of a lack of precise information on most factors involved, and on the significance of the relations between these factors and still unknown factors. In the following chapters some variables influencing the prognosis of the disease have been studied in more detail. The group of low-grade malignant lymphomas, in particular the follicular centre cell tumours, are characterized by a heterogeneous clinical behaviour. Attempts to define subgroups with a uniform clinical course on either immunological grounds, cytokinetic data, or the clinical stage have not been very successful. In the chapters II and III the significance of a more precise histocytological analysis for the prognosis under therapy is presented. In the treatment of high-grade malignant lymphomas the lack of results has led to a progressive intensification of chemotherapy regimens. Factors like histology and immunological markers did not seem to have a really important role until now. The most important condition was to achieve a complete remission, giving a better chance for prolonged survival and eventually cure. The moderate improvements with aggressive chemotherapy now show that some cytologically defined subgroups have a different course under therapy, and also that the amount of total tumour load is important for the results of treatment. However, the intensive chemotherapy protocols needed have a high treatment related toxicity, and the initial survival is also reduced by a high mortality rate. Side effects often prevent effective therapy because dose reduction or lengthening of the interval between the courses have to be instituted. Since at the start of the study the most important prognostic factors in high-grade NHL seemed to be the tumour mass and the induction of a CR, a new induction regimen was developed on the basis of the studies of Skipper et al .138 This combined pulse administration of corticosteroids and S-phase specific drugs, preceding conventional therapy. The purpose was to achieve a fast initial tumour load reduction with less toxicity, as described in chapter IV. The individual responses to identical chemotherapy is variable because of insufficient pharmacokinetic and cell kinetic data. Cell kinetic data in non-Hodgkin's lymphoma are limited because representative material is difficult to obtain. Polyamine excretion in urine can give information about cell growth and cell break down processes. When polyamines are determined in all spontaneous voided urine samples, this can be used as a continuous monitoring model of tumour cell kinetics. We attempted with such a model to obtain information on the individual responses to the cytostatic drugs used in the treatment regimen of the foregoing chapter. In chapter V the results are described of polyamine measurements before and during treatment with S-phase specific drugs of patients with a high-grade malignant lymphoma. ... Zie: Summary