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Autologous Bone Marrow Transplantation - Blog Science Connections

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Intensification Regimens for<br />

<strong>Autologous</strong> <strong>Bone</strong> <strong>Marrow</strong> <strong>Transplantation</strong><br />

Emil Frei III, Carol A Cucchi, and Beverly Teicher<br />

Intensification chemotherapy and total body radiotherapy have been curative<br />

for some patients with hematologic malignancies; accordingly, they are<br />

under increasing study for these diseases and also, more recently, for solid<br />

tumors. The construct of intensification regimens has been largely empirical<br />

and provides a major challenge to progress in autologous bone marrow<br />

transplantation. In this chapter we discuss the development and study of<br />

preclinical models designed to provide information that will help us to<br />

construct such intensification regimens to treat human cancers.<br />

IN VIVO MODEL<br />

Quantitative models of dose intensification into the range required for<br />

marrow transplantation have been limited. A relevant method is presented in<br />

Figure 1. Inbred mice bearing a measurable transplanted tumor are treated<br />

with a single injection of a given drug with a dose ranging upward from the<br />

LD 1 0<br />

. Since toxicity and death from most antitumor agents are delayed,<br />

excision of the tumor at 24 hours for quantitative study is possible. Important<br />

aspects of the physiologic pharmacology have been completed by 24 hours,<br />

and intracellular events will continue to occur whether the tumor is left in<br />

place or excised for quantitation. The excised tumor may be analyzed by in<br />

571

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