A study on the induction of differentiation of human leukemic cells by harringtonine combined with cytarabine.

Both harringtonine (Harr) and Ara-C are effective for treatment of ANLL. Since it was suggested that Harr could induce leukemic cells to differentiate and Ara-C might be a weak inducer of leukemic cell differentiation, we investigated the effect of Harr in combination with Ara-C on inducing differentiation of leukemic cells. Ten patients with ANLL were treated with low dose Harr in combination with low dose Ara-C. Complete remission was achieved in 8 of the 10 patients. After therapy, severe pancytopenia and moderate myelosuppression occurred in two patients who achieved remission. Four patients demonstrated a decrease in blast cells with an associated transient increase in mature granulocytes during therapy. Auer bodies appeared in 7-8% mature granulocytes in peripheral blood and in bone marrow on the 14th day of combination therapy in one patient. Freshly isolated leukemic cells from six pretreatment patients were cultured in liquid in the presence of Harr in combination with Ara-C. Apparent evidence of differentiation of leukemic cells and Auer bodies in the cytoplasm of mature granulocytic cells were observed in two of the six patients. The above results seem to suggest that the therapeutic effect of low dose Harr plus low dose Ara-C may result from both differentiation induction and cytotoxicity of the leukemic cells.