Prognostic significance of early response to a single dose of asparaginasein childhood acute lymphoblastic leukemia

Purpose: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the corr elation between in vitro and in vivo antileukemic response and long-term ou tcome were prospectively evaluated. Patients and Methods: Two hundred fifty-one patients were randomized to rec eive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthe mi [Erwinia], or pegaspargase). In vitro assessment of efficacy was express ed as the percent total cell kill (TCK), based on the number of viable cell s found after 5 days of culture in the presence of asparaginase. In vivo le ukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after trea tment 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 asparaginas e. 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%, respe ctively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leuke mic events among 21 in vitro nonresponders; 57% P < 0.001). There was no di fference in acute toxicity among the three asparaginase preparations. Conclusions: All three asparaginase preparations produced equivalent LCKs i n in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor.