Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia.


Journal Article

PURPOSE: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated. PATIENTS AND METHODS: Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK), based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment. RESULTS: There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli, Erwinia, and pegaspargase were 31%, 39%, and 36%, respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli, Erwinia, and pegaspargase were 69%, 74%, and 65%, respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders; 57%, P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations. CONCLUSIONS: All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor.

Full Text

Duke Authors

Cited Authors

  • Asselin, BL; Kreissman, S; Coppola, DJ; Bernal, SD; Leavitt, PR; Gelber, RD; Sallan, SE; Cohen, HJ

Published Date

  • January 1999

Published In

Volume / Issue

  • 21 / 1

Start / End Page

  • 6 - 12

PubMed ID

  • 10029805

Pubmed Central ID

  • 10029805

International Standard Serial Number (ISSN)

  • 1077-4114

Digital Object Identifier (DOI)

  • 10.1097/00043426-199901000-00003


  • eng

Conference Location

  • United States