Abstract: |
The success of autologous bone marrow transplantation for B cell lymphoma may depend on the efficacy of in vitro purification of patients’ tumor cell-contaminated marrow. In this study, we tested the toxicity of seven different chemotherapeutic agents against two B cell lymphoma lines (LY-16 and SK-DHL-2) as compared to normal human bone marrow granulocyte-macrophage progenitor cells (CFU-GM). 4-Hydroper-oxycyclophosphamide (4-HC), VP-16-213 (VP-16), nitrogen mustard, and vincristine showed a highly selective toxicity against cultured lymphoma cells; i.e., at doses sufficient to induce a 4-log clonogenic tumor cell reduction (4-HC 21 μg/ml, VP-16 50 μg/ml, nitrogen mustard and vincristine 5 μg/ml), 10.0±6.7, 3.0±3.2, 23.2 ±22.7 and 24.0 ± 17.0% (mean ± 1 SD), respectively, of normal bone marrow CFU-GM were preserved. The differential sensitivity of tumor cells and normal hematopoietic precursors was less prominent after exposure of cells to m-diamminechloroplatinum II (c/s-platinum); thus, at a drug dose of 100 μg/ml, all detectable lymphoma cells could be eradicated (i.e., ≥4 log reduction) while a CFU-GM recovery of only 0.2 ± 0.2% was observed. In contrast, adriamycin and bleomycin, at the highest tumoricidal concentrations tested (5 and 100 μg/ml, respectively) did not exhibit a selective toxicity toward lymphoma cell lines. In summary, our results suggest that nitrogen mustard and vincristine, as well as 4-HC and VP-16, may be useful agents for the ex vivo treatment of bone marrow grafts form B cell lymphoma patients. © 1988 S. Karger AG, Basel. |