Proposals for the objective indices for evaluating the differentiation of leukemic cells by all-trans retinoic acid in the patients with acute promyelocytic leukemia

: All-trans retinoic acid (ATRA) is widely used as a differentiation-inducing agent for acute promyelocytic leukemia (APL). However, one of the problems with this therapy is the difficulty in evaluating the extent of differentiation of leukemic cells. To determine objective indices for differentiation which can be used for judging complete remission, we treated 18 patients with acute promyelocytic leukemia, and performed sequential analysis of bone marrow, karyotype, RAR alpha gene rearrangement and PML-RAR alpha fusion gene transcript. The karyotype, RAR alpha rearrangement and PML-RAR alpha transcript returned to a normal pattern on days 31, 2, 34.8 and 47.6, respectively. We defined and analyzed maturation index (MI) by bone marrow findings as follows; (metamylocyte + band neutrophil + segmented neutrophil) (%)/(myeloblast + promyelocyte + myelocyte) (%). MI increased along with the differentiation of leukemic cells, and the days for MI exceeding 2 well correlated with the normalization of karyotype. These results suggested that MI can be used as an index of differentiation during ATRA therapy.