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 (Eschcrichia 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.
(C) 1999 Lippincott Williams & Wilkins, Inc.