One of the objectives of gerontological research is to achieve, reproducibly and at will, a verifiable discrepancy between the chronological and biological age of organisms. To accomplish this, the experimenter must be in a position to measure biological age independently. In theory, this can be done in the three ways: by actuarial analysis of large populations, assessment of overall morbidity, or observation of chronic degenerative changes that can be actually measured or graded according to a scale. Of these three approaches, only the last appears to be promising in experimental research. However, not all progressive degenerative changes represent practically useful parameters of biological age. Criteria for their evaluation are presented, and their theoretical prerequisites as well as concrete applications discussed. In a more general way, one has to be aware that biological age is a statistical entity. It cannot be directly observed but only inferred from quantifiable epiphenomena, and is, as such, not measurable like temperature or weight.
In a prospective multicenter trial the efficiency of the response-adapted COP-BLAM/IMVP-16 protocol to induce complete remissions (CR) in high-grade malignant non-Hodgkin's lymphomas as well as the prognostic relevance of adjuvant radiotherapy were investigated. From 1986-1989, 548 patients (median age 56 years) with stage II-IV (Ann Arbor) disease were treated with five cycles of COP-BLAM followed by two cycles of IMVP-16. If only a partial remission was obtained at the time of first restaging (RS) after three cycles (delayed response), treatment was switched to IMVP-16 (two to five courses) immediately. Patients achieving CR by the second RS after chemotherapy were randomized to adjuvant radiotherapy or observation. Responses to chemotherapy were 63% CR in patients completing the second RS (N = 350) or 72% if patients achieving late CR by consolidating radiotherapy are added; responses were 58% or 65% if all deaths prior to the second RS are included (N = 50). Overall and relapse-free survival were 71% and 68% at one year and 63% and 61% at two years. Multivariate risk factor analysis proved the early (by first RS) CR response to possess predominant prognostic relevance for survival. A significant advantage of adjuvant radiotherapy over no further treatment for duration of CR is not yet discernible. These results emphasize the importance of a rapidly achieved CR, thus contributing to the design of future trials.
The Kiel classification of non-Hodgkin lymphomas (NHL) has established chronic lymphocytic leukemia (B-CLL) and immunocytoma (LP-IC) as separate entities of low-grade malignant NHL by morphological and immunohistochemical criteria. The clinical and prognostic relevance of this discrimination was evaluated in a prospective multicenter observation study by the Kiel Lymphoma Study Group. From 1975 to 1980, 430 previously untreated patients with B-CLL (n = 217) and LP-IC (n = 213)a were recruited and followed for up to 14 years. While the age and sex distribution and the incidence of clinical stages were quite similar in both entities major differences between initial manifestations in B-CLL and LP-IC became evident, e.g. in the incidence of bone marrow infiltration (99.5 vs. 86%), peripheral blood lymphocytosis (99.5 vs. 60%), or monoclonal gammopathy (1 vs. 30%). A strictly localized tumor (Ann Arbor stage I/IE) was seen in only 1.5% of the LP-IC patients who were successfully treated by local radiotherapy. In all other patients an expectative-palliative treatment concept was pursued. Long-term survival data analysis revealed significant differences between B-CLL and LP-IC and identified the pseudofollicular in B-CLL and the lymphoplasmacytic in LP-IC as the most favorable histological subtypes. The discriminative prognostic potential of clinical stage (Rai or Binet classification) for B-CLL and LP-IC varied and the pattern of prognostic risk factors obtained by multivariate analysis was not identical. Thus, the morphological distinction between B-CLL and LP-IC correlates with characteristic differences between these entities both in their initial clinical presentation and long-term prognosis.
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