High-dose methylprednisolone, low-dose cytosine arabinoside, and mitoxantrone in children with myelodysplastic syndromes.

High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML), therefore we used HDMP in the treatment of four children with myelodysplastic syndrome (MDS). Two patients had refractory anemia with an excess of blasts in transformation (RAEB-t) with extramedullary infiltration (EMI), one had chronic myelomonocytic leukemia with pleural effusion, and one had RAEB. HDMP was administered orally at a single dose of 20-30 mg/kg/day combined with low-dose cytosine arabinoside (LD Ara-C) (10 mg/m2, 12-hourly s.c.) for 2 weeks. The treatment continued with mitoxantrone (10 mg/m2, i.v.) and Ara-C (5 mg/kg, i.v.) once a week for four doses followed by maintenance chemotherapy. All patients achieved hematologic remission 2-4 weeks after initiation of treatment. Extramedullary infiltration disappeared in all cases within 2 weeks to 3 months after initiation of therapy. With the exception of two patients who relapsed 6 and 24 months after remission, treatment could be stopped in others who remained in remission for 36 months without evidence of EMI; 6 months later one of them developed myelodysplastic relapse (RAEB). No side effects related to HDMP treatment were noted, but hyperleukocytosis developed in two patients who initially had high WBC counts. We suggest that the addition of HDMP with or without LD Ara-C to cytotoxic chemotherapy offers a promising alternative in cases not considered suitable for bone marrow transplantation.