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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1709-1715
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Weekly polyethylene glycol conjugated L-asparaginase compared
with biweekly dosing produces superior induction remission rates in
childhood relapsed acute lymphoblastic leukemia: a pediatric oncology
group study
Thomas C. Abshire,
Brad H. Pollock,
Amy L. Billett,
Patricia Bradley, and
George R. Buchanan
From Emory University School of Medicine, Atlanta, GA;
Pediatric Oncology Group Statistical Office and the University of
Florida College of Medicine, Gainesville, FL; Harvard Medical School,
Boston, MA; Enzon Inc, Piscataway, NJ; and University of Texas
Southwestern Medical Center, Dallas, TX. A list of the institutions
that participated in the study appears at the end of this article.
The relapse rate in childhood acute lymphoblastic leukemia (ALL) is
approximately 30% but few reinduction regimens have investigated the
intensive use of polyethylene glycol Escherichia coli
asparaginase (PEG-Asp). Therefore, we assessed the pharmocokinetics and
efficacy of PEG-Asp in this setting. Children with B-precursor ALL, in first marrow and/or extramedullary relapse were eligible. Reinduction included doxorubicin on day 1, prednisone for 28 days, vincristine weekly for 4 weeks, and PEG-Asp either weekly or biweekly by
randomization. Asparaginase levels and antibody to both E
coli asparaginase and PEG-asp were measured weekly just before
each PEG-asp dose. Overall, 129 of 144 patients (pts) (90%) achieved a
complete remission (CR). There was a highly significant difference in
CR rates between weekly (69 of 71; 97%) and biweekly (60 of 73; 82%)
PEG-Asp dosing (P = .003). Grade 3 or 4 infectious
toxicity was common (50%), but only 4 pts died of sepsis during
induction. Other toxicities were infrequent and hypersensitivity was
rare (6 of 144; 4%). Low asparaginase levels were associated with high
antibody titers to either native (P = .024) or PEG asp
(P = .0013). The CR rate was significantly associated
with higher levels of asparaginase (P = .012). Patients
with ALL in first relapse receiving weekly PEG-Asp had a higher rate of
second remission compared with biweekly dosing. Low levels of
asparaginase were associated with high antibody titers. Increased
asparaginase levels may correlate with an improved CR rate. The use of
intensive PEG-Asp should be explored further in the treatment of ALL.
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