International Journal of Cell Cloning, Vol 9, 503-510, Copyright © 1991 by AlphaMed Press
Elimination of clonogenic tumor cells from bone marrow using methylprednisolone (MP) and etoposide VP16: an in vitro pharmacologic study
G Miller, T Brashear, M Stone and J Fay
Division of Hematology-Oncology, Baylor University Medical Center, Charles A. Sammons Cancer Center, Dallas, Texas 75246.
The ability to eliminate malignant cells from bone marrow (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 (VP16) alone or in combination on 5
tumor cell lines (HL-60, a promyelocytic cell line; Molt-4, a T cell
leukemia; Daudi, a Burkitt's lymphoma and R10/8226 and R40/8226,
doxorubicin-resistant 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 microM, 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.
