Autologous Bone Marrow Transplantation - Blog Science Connections

572 Clinical Intensification Regimens forABMT
Figure 1. In vivo model of high-dose intensification regimen. Abbreviations: LD :o, lethal
dose; CP, cisplatin.
vitro cloning or by quantitative assay in inbred strains (l;Teicher et ai,
unpublished data).
Figure 1 presents data with respect to the action of cisplatin and BCNU
(carmustine) in a transplantable fibrosarcoma. The LD 1 0
of cisplatin
produces a less than 1 log cell kill; that is, enough to result in transient tumor
regression. With increasing doses, up to 3- to 5-fold the LD-i 0, an exponential
increase in log kill is achieved. The slope for carmustine is less steep, but it
still maintains the log linear relationship between cell kill and dose.
Using this model, we have demonstrated in three different tumor systems
that the alkylating agents maintain a linear log relationship between dose and
cell kill down through 4-5 logs (the limit of the assay). For nonalkylating
agents, and particularly for cell cycle-sensitive agents, the killing curves are
curvilinear, producing marginal increments in cell kill at higher doses. This
system has demonstrated clearly that alkylating agents have properties