Abstract
Remission-induction chemotherapy of adult acute nonlymphocytic leukaemia (ANLL) with the new EORTC protocol LAM-6 includes Daunorubicin (DNR) as the anthracycline instead of Adriamycin, which was included in previous protocols. This choice was made in order to reduce bone marrow toxicity while maintaining the antileukaemic effect. In this study, the tissue concentrations of DNR and its metabolites in nucleated bone marrow and peripheral blood cells were investigated, together with the plasma pharmacokinetics, as measured with High Pressure Liquid Chromatography (HPLC). In 5 ANLL patients studied, during 3 repetitive injections of DNR, accumulation of DNR and its major metabolite was observed in plasma and blood leukocytes. In bone marrow, a considerable variation of DNR concentrations was found (tissue levels of DNR: 0.44 x 10-5M — 6.36 x 10-M and of Daunomycinol: 1.33 x 10-5M — 10.0 x 10-5M). In one patient no drug was detectable in bone marrow. Evidently, no correlation could be observed between bone marrow concentrations and plasma concentrations of DNR. Also, in patients studied during a second induction course, the cellular concentrations of DNR in hypoplastic bone marrow were different, when compared with the initial treatment. This study demonstrates that bone marrow concentrations of DNR have large individual variation, which may be indicative for the outcome of therapy.
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