Cytogenetic studies indicate that the majority of patients with acute leukemia have cytogenetic abnormalities in their leukemic cells; such abnormalities are constant within a given patient, though not for acute leukemia as a disease. The fact that the same cytogenetic abnormalities reappear after relapse from complete remission indicates that relapse is a function of regrowth of persistent leukemic cells. It was demonstrated in the experimental mouse leukemia model system L1210 that unless all of the leukemic cells are destroyed, death will result from leukemia. Prior to treatment (and during relapse), it is estimated that the average child with acute leukemia has approximately 1012 leukemic cells. In the L1210 model, it was demonstrated that the size of the inoculum of leukemic cells determines the time of death and that the percentage of leukemic cells killed (fractional kill) with a given dose is constant regardless of the size of the inoculum. Thus, the number of neoplastic cells present at the time of a given treatment critically influences the chances of eliminating all the cells. In this model with a short generation time, intensive short term treatment is more effective in reducing the number of leukemic cells.
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|Published - 1973