When is autologous bone marrow transplantation safe after high-dose treatment with etoposide?

Etoposide (VP16-213) is widely used in the treatment of malignant disease and increasingly high doses are now used in conjunction with autologous bone marrow transplantation. After treatment with etoposide, bone marrow should be reinfused as soon as the plasma etoposide concentration has fallen to a level which will not prove toxic to the small number of pluripotential stem cells present in the reinfused marrow, but this level has not been previously defined. Nine patients were studied of whom five received 1400 mg etoposide/m2 and four received 2400 mg etoposide/m2 intravenously over 3 days. Bone marrow was reinfused 64-136 h after finishing chemotherapy. Haemopoietic recovery occurred in all patients within 16 days of autologous bone marrow reinfusion performed at a time when plasma etoposide concentrations ranged from 0-2.42 micrograms/ml. However the clinical and in vitro data presented suggest that bone marrow reinfusion after treatment with high-dose etoposide should be delayed until the plasma etoposide concentrations have fallen to less than 0.4 microgram/ml although haemopoietic recovery may occur after bone marrow reinfusion at higher concentrations.