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

T. C. Abshire, B. H. Pollock, A. L. Billett, P. Bradley, G. R. Buchanan

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

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. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)1709-1715
Number of pages7
JournalBlood
Volume96
Issue number5
StatePublished - Sep 1 2000

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Remission Induction
Asparaginase
Pediatrics
Oncology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Escherichia coli
Recurrence
Toxicity
Antibodies
Vincristine
Random Allocation
Prednisone
Doxorubicin
Polyethylene glycols
Sepsis
Hypersensitivity
Bone Marrow

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Abshire, T. C.; Pollock, B. H.; Billett, A. L.; Bradley, P.; Buchanan, G. R.

In: Blood, Vol. 96, No. 5, 01.09.2000, p. 1709-1715.

Research output: Contribution to journalArticle

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abstract = "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. (C) 2000 by The American Society of Hematology.",
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