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.
RCT Entities:
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.
Authors: S-H Chen; W Yang; Y Fan; G Stocco; K R Crews; J J Yang; S W Paugh; C-H Pui; W E Evans; M V Relling Journal: Leukemia Date: 2010-11-12 Impact factor: 11.528
Authors: Naina Patel; Shekhar Krishnan; Marc N Offman; Marcin Krol; Catherine X Moss; Carly Leighton; Frederik W van Delft; Mark Holland; Jizhong Liu; Seema Alexander; Clare Dempsey; Hany Ariffin; Monika Essink; Tim O B Eden; Colin Watts; Paul A Bates; Vaskar Saha Journal: J Clin Invest Date: 2009-06-08 Impact factor: 14.808
Authors: P Kaaijk; G J L Kaspers; E R Van Wering; G J Broekema; A H Loonen; K Hählen; K Schmiegelow; G E Janka-Schaub; G Henze; U Creutzig; A J P Veerman Journal: Br J Cancer Date: 2003-03-10 Impact factor: 7.640
Authors: L B Silverman; K E Stevenson; J E O'Brien; B L Asselin; R D Barr; L Clavell; P D Cole; K M Kelly; C Laverdiere; B Michon; M A Schorin; C L Schwartz; E W O'Holleran; D S Neuberg; H J Cohen; S E Sallan Journal: Leukemia Date: 2009-12-17 Impact factor: 11.528