Changes in drug delivery (by blood-brain barrier dysfunction) on arachnoid leukemia: implication for CNS leukemic dissemination.

The infiltrates of intracerebrally inoculated DBLA-6 leukemia cells of the rat were used as an experimental model of meningeal leukemia in acute leukemia. Systemic administration of an antileukemic agent (daunomycin) started at the early stage of the leukemic involvement in the arachnoid, when the blood-brain barrier (blood-cerebrospinal fluid barrier) was not yet broken in the pial microcirculation. In those animals in which the antileukemic agent alone was administered, leukemic infiltration was decreased in the dura while it was clearly observed in the subarachnoid space. In those animals in which the blood-brain barrier was damaged by acute angiotensin-induced hypertension, the chemotherapeutic effect on leukemic infiltration was markedly enhanced in the arachnoid and other parts of the brain. The blood-brain barrier dysfunction was analysed using the technique of fluorescein cine-angiography. The results indicated that the chemotherapeutic effect of the agent given systemically was impeded by the barrier, particularly in early arachnoidal infiltration of leukemic cells. Also, this in vivo experiment showed the importance of drug delivery to tumor cells growing outside blood vessels in cancer chemotherapy.