[Pharmakokinetics of hydroxy-urea. Therapy of acute myeoblastic leukemias using synchronization and recruitment...

By a plasma-concentration of hydroxy-urea (HU) higher than 0.5-2.2x10(-4)M the DNA-synthesis in leukemia cells was blocked reversibly in 9 patients. The plasma half-time of HU varied between 120 and 198 min. To synchronize leukemic cell populations the DNS-synthesis was blocked over a period of 36 hours by maintaining the HU-concentration above the critical lower level. In a second phase-specific therapeutic step cytosine-arabinoside (AraC) was given 4 times in a dose of 1 mg/kg each. A recruitment after the application of AarC made more cells available for the next following synchronization step. 4 acute myeloblastic leukemias with high peripheral cell counts were treated according to this schedule. One patient is still in complete remission for now 14 month. This synchronization/recruitment schedule seems to be successful in acute myeloblastic leukemias with high proliferation rates measured by biochemical and cytokinetic methods.