Recruitment of quiescent tumor by humoral stimulatory activity: requirements for successful chemotherapy.

Acute leukemia is a heterogeneous tumor with respect to cellular proliferation and is sensitive to positive and negative growth control factors. Tumor associated inhibitory activity (TAIA) and simultaneously present humoral stimulatory activity (HSA) in this disease may be modulated by timed sequential chemotherapy to increase tumor growth at a predictable time and make it more sensitive to accurately administered drug. Our in vivo studies of timed sequential chemotherapy in human leukemia demonstrate than an increase in tumor labeling index (LI) temporally coincides with the detection of HSA following drug administration. Maximal HSA occurs at a predictable time following initial administration of the aplasia-producing drug and is coincident with an increased LI of recovering normal marrow granulocytic elements and marrow tumor cells. These studies demonstrate the salutary effect of drugs given in high dose to reduce tumor mass and recruit tumor cells to further high-dose drug sensitivity.