Differentiation and Apoptosis inducing Therapy with High-dose Methylprednisolone for non-APL Acute Myeloblastic Leukemia

Considerable progress has been achieved in the treatment of patients with acute promyelocytic leukemia (APL) by using retinoic acid and/or arsenic trioxide. However, it is generally considered that an effective agent which induces differentiation of myeloid leukemic cells has not been provided for the treatment of patients with other subtypes of acute myeloblastic leukemia (AML). On the other hand, several in vitro studies have shown that certain steroid hormons (dexamethasone, prednisolone, methylprednisolone) induce differentiation of some mouse and human myeloid leukemic cells to macrophages and granulocytes. We have also shown that short-course (3 to7 days) high-dose methylprednisolone (HDMP, 20-30 mg/ kg) treatment can induce terminal differentiation of myeloid leukemic cells in children with APL and in other subtypes of AML (AML-M1, AML-M2, AML-M4 and AML-M7). HDMP has also been shown to induce apoptosis of myeloid leukemic cells in different subtypes of AML in vivo and in vitro. After short-course (3 to 7 days) HDMP treatment alone, in addition to rapid clinical improvements, decreases in blast cells in both peripheral blood and bone marrow and dramatic reductions in the size of myeloid tumors were observed. HDMP combined with mild chemotherapy increased the remission rate (87-89%) and improved the outcome of the patients.