成人急性白血病の細胞回転に及ぼすCytosine Arabinosideの影響

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The in vivo effects of a single intravenous dose of 5 mg/kg cytosine arabinoside (CA) were studied on the mitotic cycle of leukemic cells and erythroblasts in the bone marrow from 8 adult patients with various types of acute leukemia. The results were correlated with response to the subsequent therapy with CA alone or combined with prednisolone or 6MP.
The in vitro ³H-thymidine labeling index (LI) and mitotic index (MI) of leukemic cells showed a significant decrease 4 hours after injection of CA and a tendency to recover within 48 hours in all cases studied. However, in only 3 cases where complete remission could subsequently be attained, the LI of leukemic cells at 48 hours returned nearly to or exceeded the pretreatment level. Whereas the value as high as three times the pretreatment level was initially observed in one out of the 3 cases, the LI at 48 hours remained below the pretreatment level when the test was repeated on relapse which was proved refractory to the CA therapy. These results suggest that partial synchronization of leukemic cells in DNA synthesis and/or recruitment of the cells from the resting state into the mitotic cycle can be achieved after a single injection of CA in some cases, and that these two mechanisms may lead to the success of the intermittent CA therapy.
A marked increase in the percentage of erythroblasts was found 48 hours after injection of CA in the bone marrow from 3 patients. This finding, which may have been caused by a decrease of leukemic cells as well as an increse of erythroblasts, appeaers to be significant in predicting the effectiveness of the CA therapy, since while in 2 out of 3 cases complete remission could be attained by subsequent CA therapy, no significant increase in the percentage of erythroblasts was found in other cases unresponsive to the CA therapy.