In vivo cellular adriamycin concentrations related to growth inhibition of normal and leukemic human bone marrow cells

Abstract

Inhibition of clonogenicity of normal and leukemic human hematopoietic progenitor cells was studied after in vivo and in vitro exposure of bone marrow to adriamycin (ADM). Flow cytometric determination of cellular ADM concentrations in blast cells, expressed in fluorescence units/cell (FU/cell), correlated well with the extent of cytotoxicity. After 2 h in vitro exposure to 500 ng ADM/ ml, the ADM concentration of leukemic ( n = 7) and normal ( n = 4) bone marrow blast cells amounted to 231 ± 180 and 249 ± 53 FU/cell respectively, producing moderate decreases in clonogenicity by 44 ± 30 and 54 ± 27%. Exposure to 2000 ng/ml produced ADM concentrations of 1184 ± 472 FU/cell for leukemic blast cells and 1024 ± 281 FU/cell for normal blast cells. Inhibition of clonogenicity was 96 ± 7% in leukemic blasts and 99 ± 1% in normal blasts. In vivo ADM concentrations in leukemic blast cells at 1–2 h after administration were 216 ± 98 FU/cell ( n = 8 patients). This implies that inhibition of clonogenicity after administration of conventional dosages of ADM will be approx. 60–70% for both leukemic and normal bone marrow progenitor cells. Such values were noted in four patients of whom bone marrow was cultured, which was obtained shortly after ADM monotherapy.