A novel approach to treatment in childhood acute myeloblastic leukemia and myelodysplastic syndrome with high-dose methylprednisolone as a differentiation- and apoptosis-inducing agent of myeloid leukemic cells.

Differentiation-inducing therapy with all-trans retinoic acid significantly improved the outcome in children with acute promyelocytic leukemia (APL). Therefore, use of agents that induce differentiation of leukemic cells in non-APL children appears to be a highly promising therapeutic approach. Based on the experimental studies in mice, we have shown that short-course high-dose methylprednisolone (HDMP) treatment can induce terminal differentiation of leukemic cells in children with various subtypes of acute myeloblastic leukemia (AML-M1,-M2,-M3,-M4,-M7). It has also been shown to induce apoptosis of myeloid leukemic cells with or without differentiation. Administration of HDMP as a single agent resulted in a rapid clinical improvement, a marked decrease in blast cells in both peripheral blood and bone marrow and dramatic decreases in the size of extramedullary leukemic mass in children with AML and myelodysplastic syndrome (MDS). Addition of HDMP to cytotoxic chemotherapy regimens increased the remission rate and improved the outcome in these children. Future clinical trials with HDMP would contribute to further improvements in the treatment results in these children.