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Since the differentiating effect of high-dose methylprednisolone (HDMP) on myeloid leukemic cells has been shown in one of our patients with acute myeloblastic leukemia (AML-M4), 27 previously untreated children with AML were given HDMP (20-30 mg/kg per day) combined with cytosine arabinoside (Ara-C; 3 mg/kg) for the first 2 weeks of induction therapy. Marked clinical improvement was observed in all patients with the exception of one who died within 24 hours of the treatment. Enlarged liver and spleen (greater than 5 cm) became nonpalpable in 3 (37%) out of 8 and 5 (100%) out of 5 patients, respectively, and bone marrow blasts decreased below 5% in 7 patients (27%) within 2 wk of HDMP and Ara-C treatment. Adriamycin (1 mg/kg) was added 2 wk after initiation of induction therapy. Twenty-two (84.6%) of the 26 patients achieved complete remission, 3 (11.5%) had partial remission and no response was obtained in one. Treatment was well tolerated. The addition of HDMP as a differentiating and/or cytolytic agent to conventional anti-leukemic chemotherapy increased the complete remission rate and prolonged the duration of remission of our AML patients.

High-dose methylprednisolone therapy (HDMP) induces acceleration of leukocyte recovery in acute lymphoblastic leukemia (ALL) and the differentiation of myeloblasts to mature granulocytes in acute myeloblastic leukemia (AML). These effects of corticosteroids have been shown to be due to the enhanced colony-stimulating activity (CSA) and responses to corticosteroids in some patients with aplastic anemia and myelodysplastic syndromes (MDS) have been related to increased CSA activity. We measured the serum (granulocyte-macrophage colony-stimulating factor (GM-CSF) levels by a sandwich linked immunoabsorbent assay (ELISA) in patients with ALL and AML at presentation and following high-dose methylprednisolone (HDMP) therapy. Serum GM-CSF levels at presentation in the ten cases studied ranged between 160 and 700 pg/ml (mean 418.5 ± 252.5). One week following HDMP therapy GM-CSF levels increased to between 260 and 950 pg/ml (733.5 ± 203.2). Four weeks after therapy the GM-CSF levels increased to between 470 and 1350 pg/ml (911 ± 278.7). GM-CSF levels were markedly elevated one week after HDMP in the patients with ALL, suggesting that in addition to the lymphotoxic effects on leukemic blasts, the acceleration in neutrophil recovery may be due to release of GM-CSF induced by HDMP and its effects on myeloid progenitors.