Abstract
During a 15-month period, we used in vivo bromodeoxyuridine (BUDR) infusion to study cell kinetics in 112 consecutive patients with various types of malignant tumours: acute leukaemia (50 patients), gastric cancer (42) and brain gliomas (20). The in vivo BUDR method requires that a single tumour sample be taken 4-6 h after infusion and that bivariate flow cytometry (FCM) be employed to measure simultaneously the percentage of BUDR-labelled cells (which are identified with a green fluorescent anti-BUDR monoclonal antibody) and their mean DNA content (following propidium iodide staining). This technique rapidly furnishes the labelling index (LI) and the DNA synthesis time (TS), from which the tumour potential doubling time (Tpot) and production rate (fractional turnover rate, FTR) are calculated. The procedure took 6-9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and 80 (72%) of the 112 patients, respectively. Correlations were sought between kinetic parameters and a number of pathological and clinical ones. In 34 patients with acute non-lymphoblastic leukaemias who were uniformly treated for remission (CR) induction and maintenance, proliferative activity, as measured by Tpot and FTR, was greater in responsive than in non-responsive patients, and in those who experienced CR for over 8 months than in those who had a shorter CR. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease. No correlations between kinetic and clinical and pathological parameters were found in gliomas. These data indicate the in vivo BUDR infusion coupled with FCM measurements can be performed in clinical settings to obtain kinetic data rapidly in quite large patient series. This will probably allow the inclusion of kinetic data in clinical trials aimed at evaluating the prognostic relevance of these data.
Highlights
We report here the kinetic data with some clinical correlations, obtained with this method in 112 consecutive patients with acute leukaemia (AL), malignant gastric and brain tumours
From September 1986 to January 1988, 112 consecutive patients with acute leukaemia (AL), malignant gastric and brain tumours received in vivo BUDR infusion for kinetic studies before cell specimens were obtained for diagnostic purposes, including cytological and histological examination
The cytogram of Figure lb is representative of the BUDR and DNA distribution in a tumour specimen taken for both labelling index (LI) and TS determinations 6 h following BUDR infusion
Summary
From September 1986 to January 1988, 112 consecutive patients with acute leukaemia (AL), malignant gastric and brain tumours received in vivo BUDR infusion for kinetic studies before cell specimens were obtained for diagnostic purposes, including cytological and histological examination. Administration of BUDR was authorised by the Ethical Committee at the Department of Internal Medicine of the University of Pavia, and written informed consent was obtained from each patient. Two to 4 mm diameter tumour samples were obtained during surgery in patients with gastric and brain tumours. Normal gastric mucosa was obtained from seven patients with gastric cancers (Table II)
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