Elimination of clonogenic tumor cells from bone marrow using methylprednisolone (MP) and etoposide VP16: An in vitro pharmacologic study

Publisher Website
Google Scholar
Abstract
The ability to eliminate malignant cells from bone marro (BM>while retaining sufficient numbers of normal progenitors to ensure. Engraftment, may well establish the future of autologous BM transplantation (ABMT) for hematologic malignancies. In this study, we describe the effects of methylprednisolone (MP) and etoposide (VPl6) alone or in combination on 5 tumor cell lines (HL-60, a promyelocytic cell line; Molt-4, a T cell leukemia; Daudi, a Burkitts lymphoma and MOB226 and R40/8226, doxorubicinresistant myeloma cell lines). The tumor cell kill efficiency of the drugs was assayed using the limiting dilution assay. We determined the toxic effect on progenitor cells by assaying granulocyte-macrophage colony- forming units (CFU). With a combination of MP at 10-3 M and VP16 at 75 μM, we observed the following log reduction in tumor cell clones: HL-60, 4.695 ± 0.001; Molt-4, 3.626 ± 0.036; Daudi, 5.633 ± 0.001; R10/8226, 3.052 ± 0.544; R40/8226, 3.126 ± 0.080. CFU recovery was 24% ± 5%. Mixing tumor cell lines with a 20-fold excess of normal irradiated BM cells did not eliminate the inhibitory effect of the drug combination. We propose that MP and VP16 used in concert produce effective purging of malignant hematopoietic cells from BM while sparing normal progenitors needed for engraftment.