Charles A. Brubaker

Predinsome therapy of acute childhood leukemia: Prognosis and duration of response in 330 treated patients

Induction of remission with prednisone in 330 children with acute leukemia resulted in improvement to complete remission in 40 per cent and in good partial remission in another 34 per cent of patients. Complete bone marrow remission occurred in 63 per cent. Remission was maintained without treatment for a median duration of 58 days. Infants under 1 year of age, patients with initially high white blood cell counts, and those with a morphologic diagnosis of acute granulocytic leukemia responded less favorably than the other children.

Varying prednisone dosage in remission induction of previously untreated childhood leukemia.

Although prednisone has been effectively used to induce remission in acute leukemia, a controlled exploration of optimal dosage and of intermittent therapy has not been reported. Of 223 previously untreated children 86 received 2 mg/kg in three divided daily doses; 85 received 4 mg/kg in three divided daily doses; 28 received 8mg/kg every other day in a single dose and 24 received 16 mg/kg every fourth day in a single dose. Steroid side effects were minimal in intermittent therapy. The percentage of remissions on these two regimes, however, was significantly lower than on continuous therapy. Bone marrow remissions were found in 21% on 8 mg/kg every other day and 12% on 16 mg/kg every fourth day. Remission rates of 72% and 60%, respectively, were obtained on the 2mg/kg and 4 mg/kg regimens, indicating no significant difference between these two groups. Continuous prednisone therapy appears to be more effective than intermittent dosage regimens in inducing remission in acute childhood leukemia.

Induction of remission in acute leukemia ofchildhood by combination of prednisone and either 6-mercaptopurine or methotrexate

A controlled study of two chemotherapeutic induction regimens in the treatment of229 patients with acute leukemia of childhood is reported. The efficacy of a combination of prednisone and 6-mercaptopurine was compared to that of prednisone and methotrexate. Complete bone marrow remission in cases of acute lymphoblastic and undifferentiated leukemia was obtained in 86 per cent with prednisone and 6-mercaptopurine and in 80 per cent with prednisone and methotrexate. In the other types of acute leukemia, marrow remissions were noted in only 33 per cent with the former, and 22 per cent with the latter regimen.

The use of combination therapy in leukemia remission

The purpose of this study by Childrens Cancer Study Group A was to explore the effectiveness of combination chemotherapy in the remission maintenance of childhood leukemia. Sixty‐four children with leukemia underwent complete remission with varying doses of prednisone, vincristine, or a combination of 6‐mercaptopurine and methotrexate. They were then treated with 8‐week alternating courses of oral 6‐mercaptopurine and methotrexate. Midway in each course of 6‐mercaptopurine, intravenous actinomycin‐D was given. Similarly, intravenous nitrogen mustard was given during each course of methotrexate. The combination therapy was well‐tolerated. Significantly longer remissions were found in those patients induced with prednisone who received the combination chemotherapy (median = 720 days) when compared with 71 simultaneously treated controls (median = 406 days).

Induction of remission in acute leukemia with prednisone and intravenous methotrexate

Summary 1. Daily oral prednisone (2 mg. per kilogram per day) and intermittent intravenous methotrexate (3 mg. per kilogram every 14 days) were used as initial therapy for 14 unselected children with acute lymphocytic or acute undifferentiated leukemia. 2. Complete or good partial remissions were noted in every case. Bone marrow remissions (M1 rating) were achieved in 8 of 14 patients by day 14 and in all patients by day 28. 3. Toxicity attributable to methotrexate was noted in only one patient, who developed mild ulcerations of the buccal mucosa.