High‐dose methylprednisolone for remission induction in hypoplastic acute myeloid leukemia

To the Editor: The effects of certain steroid hormones on mouse myeloid leukemic cells have been examined in several studies and it has been shown that they can induce differentiation ( 1) and inhibit proliferation of myeloid leukemic cells (2). A remarkable antileukemic effect has also been shown in newly diagnosed and relapsed children with various subtypes of acute myeloblastic leukemia (AML) using high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) alone (3), which could induce in vivo differentiation of myeloid leukemic cells to macrophages and granulocytes in acute promyelocytic leukemia (4) and in other subtypes of AML (5). Combined HDMP with cytotoxic chemotherapy increased the remission rate and prolonged the duration of remission of AML children (6). We report here the use of HDMP in a child with hypoplastic AML. A 9-year-old boy was admitted in December 1993 suffering from fever, pallor and weakness starting 15 d earlier. His physical findings were normal except for mild gum hypertrophy and exophtalmus of the left eye. Laboratory results included a hemoglobin level of 5.5 g/dl, white blood cell (WBC) count of 0.6 x 109/1 with 5 % blasts and platelet count of 60 x 109/l. Repeated bone marrow (BM) aspiration and BM biopsy were markedly hypocellular ( < 20 %) and showed 75% blasts which stained positive for peroxidase (French-American-British type M 1). Induction therapy was begun with oral methylprednisolone sodium succinate (MP, Prednol-L) at a single daily dose of 10 mg/kg given for 3 d. Subsequently the patient received daily 30 mg/kg and 20 mg/kg M P for 1 week each, then it was discontinued. A few hours after initiation of HDMP treatment his fever subsided and the clinical status improved dramatically. Four days after treatment the platelet count increased to normal values (60 x 109/1 vs 220 x 109/l). Since WBC count remained under 1.2 x 109/1 1 wk after treatment, recombinant human granulocyte colony stimulating factor (rh G-CSF) (Filgrastim, Roche Basel) at a dose of 10 pg/kg was added to the HDMP treatment. It was administered intravenously for 7 d and stopped. Three days after initiation of rh G-CSF, the peripheral blood WBC count increased to 9.1 x 109/1 with 91% polymorphonuclear cells. The BM aspirate obtained on the same day (10 d after HDMP and 3 d after rhGCSF) revealed normal cellularity with 2 % blasts. Then low-dose cytosine arabinoside (LD Ara-C, 10 mg/m2, subcutaneously every 12 h for 2 wk) and mitoxantrone (10 mg/m2 weekly for four doses) were added to induction therapy. Since the WBC count decreased below 2 x 109/1 after the first dose of mitoxantrone, rhG-CSF ( 5 pg/kg) was readministered daily for only 4 d, and the WBC count increased to 6.1 x 109/1 within 1 wk. Despite reinitiation of chemotherapy, the WBC count remained above 2 x 109/1 until the induction therapy was completed. No side effects of corticosteroid or rhG-CSF were seen. Treatment was continued with consolidation followed by maintenance therapy. The patient’s gingival and orbital infiltration disappeared within 2 wk of treatment. The patient is still in complete remission with normal peripheral blood and BM findings. Although there has been considerable progress in the treatment of AML with intensive chemotherapy, a very limited therapeutic approach is available for remission induction of AML patients with hypocellular bone marrow at presentation. The result in our case with HDMP is very promising. G-CSF induces the proliferation and differentiation of normal BM granulocytic precursors and it may also induce myeloid leukemic cells to terminal differentiation (7). By using HDMP combined with rhG-CSF, complete remission was described in a patient with refractory AML (8). However, in our case the role of rhG-CSF administration in such a short time (3 d) for inducing remission is very doubtful. Rather, it might have a role in increasing the peripheral blood polymorphonuclear cells. The pathogenesis of marrow hypocellularity in AML is obscure. However, it has been suggested that these patients bear a lower leukemia burden than those with classic AML and that the marrow failure ensues without “crowding out” of normal