[Principles of high-dose cytarabinoside treatment].

Ara-C can be regarded as an analogue of cytidine and of deoxycytidine. It is activated by a kinase system leading to Ara-CTP and inactivated by deaminases mainly to Ara-U. Resistance to Ara-C can develop by at least four mechanisms: decreased activation, increased inactivation, decreased half-life of intracellular Ara-CTP and decreased cellular incorporation. Following short-therm high-dose infusions, therapeutically significant concentrations in blood and cerebrospinal fluid can be achieved for 6-12 hrs. The concept of high dose Ara-C is thus based on solid biochemical and pharmacological data; its application in refractory leukemias and lymphomas and in leukemic meningeosis is, however, restricted by significant toxicity and by the reduced normal stem cell potential in these patients.