Additive therapy in the maintenance of remission in acute lymphoblastic leukemia of childhood: The effect of the initial leukocyte count

Abstract

Following introduction of M1 marrow remission in 81% or 329 of 407 patients treated with prednisone and biweekly intravenous methotrexate, 321 patients were randomly assigned to one of six maintenance treatment regimens designed to evaluate the effect of bimonthly intravenous pulses of the additives actinomycin D, nitrogen mustard, and 5‐fluorouracil on the duration of remission in acute lymphoblastic leukemia of childhood. In patients with an initial WBC below 20,000/mm3, a statistically significant beneficial effect of additives was observed in Regimen 1 (actinomycin D with 6MP, nitrogen mustard with methotrexate), Regimen 2 (actinomycin D with 6MP and methotrexate), and Regimen 6 (5‐fluorouracil with 6MP and methotrexate). Children with an initial WBC above 20,000/mm3 had the least favorable prognosis; in this group additives appeared to have an adverse effect but the difference was not significant. Survival was also significantly longer in patients with an initial WBC of less than 5000/mm3, when compared to those with an initial WBC of above 20,000/mm3. Little difference in the degree or frequency of hematologic, gastrointestinal, and hepatic toxicity was encountered in the various regimens. These results indicate that additive therapy is beneficial in those patients with the most favorable prognosis and that the prognostic effects of the initial WBC must be given careful consideration in future protocol design, patient randomization, and data analysis of controlled clinical trials. Copyright © 1974 American Cancer Society