Flow cytometric determination with bromodeoxyuridine/DNA assay of sensitivity of S-phase cells to cytosine arabinoside in childhood acute lymphoblastic leukemia.

The percentages of S-phase cells in leukemic and normal bone marrow cells and their sensitivity to cytosine arabinoside (Ara-C) were determined by in-vitro bromodeoxyuridine (BrdUrd)/DNA analysis in children with acute lymphoblastic leukemia. The lymphoblasts during relapse showed a higher proliferating activity than at the time of the diagnosis. The sensitivity of S-phase cells to Ara-C was measured by the percentages of the residual S-phase cells capable of incorporating BrdUrd after incubation with various concentration of Ara-C (1 ng-10 micrograms/ml). A constant dose response was found in the normal bone marrow cells of disease-free children who were in complete remission with a marked reduction of the S-phase population at a concentration of 100 ng/ml. In the leukemic bone marrow cells, in contrast, there was a wide variation in sensitivity to Ara-C. The sensitivity did not correlate with the proliferating activity of leukemic cells. In two patients, there was a good correlation between in-vitro sensitivity and clinical response to Ara-C.