The proliferative activity of leukaemic myeloblasts following the intravenous infusion of cytarabine.
Serial bone marrow aspirates were obtained from 16 adults with acute myeloid leukaemia (AML) before and after a single infusion of cytarabine (5.0 mg/kg i.v. over 30 min). Changes in the proliferative activity of the leukaemic myeloblasts were monitored by determination of the labelling index (LI) and the mitotic index (MI). There was a significant fall in both LI and MI within a few hours of the administration of cytarabine (P = 0.005). In 14 of the 16 cases the LI subsequently rose to observed maxima 0.3% to 14.1% (mean 5.0%) above the preinfusion LI, 11 to 77 hours (mean 40.8 h) after the infusion (P less than 0.05). The MI returned to the mean pretreatment level within the period of observation in 11 of the 16 cases. In general, the changes in MI followed those in LI; the results are consistent with cytarabine-induced arrest or death of leukaemic blast cells in S phase. Because of the variability in timing of kinetic changes in leukaemic myeloblasts following cytarabine, it is not possible to institute remission induction therapy consistently at the time of maximum synchronization with any fixed chemotherapeutic schedule. Furthermore, the degree of synchronization attained is, in general, small, limiting the prospect of exploiting synchronization with cytarabine as a means of improving the remission rate for AML.