Four-Agent Induction and Intensive Asparaginase Therapy for Treatment of Childhood Acute Lymphoblastic Leukemia


Journal Article

We prospectively assigned 289 consecutive children with acute lymphoblastic leukemia to receive one of two treatment programs on the basis of the presence or absence of certain risk factors at the time of diagnosis. Patients at high risk (62 percent of the total) had one or more of the following risk factors: age below two or above nine years, a white-cell count of 20,000 per cubic millimeter or more, the presence of T-cell immunologic markers, radiologic evidence of a mediastinal mass, and involvement of the central nervous system. Patients in both the standard-risk and high-risk groups were treated for two years, receiving intensive remission-induction therapy, central nervous system prophylaxis, weekly administration of high-dose asparaginase, and multiple-drug continuation therapy (which in the high-risk group included doxorubicin and a larger dose of prednisone). At a median follow-up of 35 months, the mean (±SE) event-free survival rates at four years among the patients in the standard-risk and high-risk groups were 86±4 percent and 71±4 percent, respectively (P = 0.003), for a total event-free survival of 77±3 percent. Within the high-risk group, the white-cell count at diagnosis and the sex of the patient were not significant prognostic indicators, but age below 12 months at diagnosis was associated with a very poor outcome. As compared with previous methods, this treatment program using four-drug induction and intensive asparaginase therapy has resulted in improved event-free survival in children with acute lymphoblastic leukemia. (N Engl J Med 1986; 315:657–63.), A REVIEW of the treatment of childhood acute lymphoblastic leukemia in the past decade suggests that prolonged disease-free survival in most studies has ranged from 50 to 70 percent.1 In a series of trials conducted between November 1973 and December 1980, we found that although the percentage of children having a complete remission remained relatively unchanged, the total number of failures diminished progressively, and the cause of failure gradually shifted, from leukemic relapse in most patients to relapse and death during remission in equal numbers of patients (Table 1).234567 On the basis of that clinical experience, we initiated protocol 81–01…. © 1986, Massachusetts Medical Society. All rights reserved.

Full Text

Duke Authors

Cited Authors

  • Clavell, LA; Gelber, RD; Cohen, HJ; Hitchcock-Bryan, S; Cassady, JR; Tarbell, NJ; Blattner, SR; Tantravahi, R; Leavitt, P; Sallan, SE

Published Date

  • September 11, 1986

Published In

Volume / Issue

  • 315 / 11

Start / End Page

  • 657 - 663

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

International Standard Serial Number (ISSN)

  • 0028-4793

Digital Object Identifier (DOI)

  • 10.1056/NEJM198609113151101

Citation Source

  • Scopus