Rationale and hematologic target points in response-oriented individualized induction chemotherapy for acute myeloid leukemia.

Abstract

Response-oriented individualized induction chemotherapy (ROIIC) has been reported to achieve a high complete remission (CR) rate in acute myeloid leukemia (AML). In ROIIC, drug dose is modified for each patient to achieve hematologic target points, based on the concept that this achievement, not a preset drug dose, increases the likelihood of attaining CR. However, the existing target points lack objectivity, therefore prohibiting worldwide use of ROIIC. In addition, the achievement of these target points does not statistically relate to CR, which contradicts the concept of ROIIC. To solve these problems, we evaluated various parameters of 117 AML cases treated by ROIIC to identify the factors relating to CR. Of 117 AML subjects, 75 achieved CR with ROIIC and most cases achieving CR did so with one ROIIC course. Not the administered dose of drugs but several hematologic parameters at the end of ROIIC correlated significantly with CR. A total of four parameters, all related to the leukemic cell mass, were independent predictive factors of CR. A formula consisting of these parameters predicted CR cases with high sensitivity (98%) and non-CR cases with high specificity (96%). Based on this formula, an objective target point (a bone marrow blast mass ratio between before and after ROIIC of below 0.15), valid for dose modification during ROIIC, was established. These results validate the concept of ROIIC and enable objective dose modification in ROIIC and universal application of this therapy. Further, the formula predicting non-CR cases at the end of ROIIC is useful for deciding early therapeutic intervention for such cases.