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


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.
Strong Children's Research Center, University of Rochester, Medical Center, NY 14642, USA.
B L
BL
Asselin
S
S
Kreissman
D J
DJ
Coppola
S D
SD
Bernal
P R
PR
Leavitt
R D
RD
Gelber
S E
SE
Sallan
H J
HJ
Cohen
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D016974:Dickeya chrysanthemi / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D011092:Polyethylene Glycols / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase