Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia

A report from the Taiwan Pediatric Oncology Group

D. C. Liang, I. J. Hung, C. P. Yang, K. H. Lin, Chien-Hsu Chen, T. C. Hsiao, T. T. Chang, C. H. Pui, C. H. Lee, K. S. Lin

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count < 10 x 109/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count < 50 x 109/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1%, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide.

Original languageEnglish
Pages (from-to)155-160
Number of pages6
JournalLeukemia
Volume13
Issue number2
DOIs
Publication statusPublished - 1999 Jan 1

Fingerprint

Remission Induction
Asparaginase
Taiwan
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Escherichia coli
Mortality
Etoposide
Leukocyte Count
Therapeutics
Hypoalbuminemia
Cytarabine
Vincristine
Prednisolone
Hyperglycemia
Disease-Free Survival
Leukemia
B-Lymphocytes
Central Nervous System
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Liang, D. C. ; Hung, I. J. ; Yang, C. P. ; Lin, K. H. ; Chen, Chien-Hsu ; Hsiao, T. C. ; Chang, T. T. ; Pui, C. H. ; Lee, C. H. ; Lin, K. S. / Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia : A report from the Taiwan Pediatric Oncology Group. In: Leukemia. 1999 ; Vol. 13, No. 2. pp. 155-160.
@article{e9fd2f2302a74af9b65c84c068f8bdc2,
title = "Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: A report from the Taiwan Pediatric Oncology Group",
abstract = "The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count < 10 x 109/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count < 50 x 109/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1{\%}, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72{\%} (95{\%} confidence interval, 55-89{\%}) and 87.2{\%} (78-96{\%}), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide.",
author = "Liang, {D. C.} and Hung, {I. J.} and Yang, {C. P.} and Lin, {K. H.} and Chien-Hsu Chen and Hsiao, {T. C.} and Chang, {T. T.} and Pui, {C. H.} and Lee, {C. H.} and Lin, {K. S.}",
year = "1999",
month = "1",
day = "1",
doi = "10.1038/sj.leu.2401260",
language = "English",
volume = "13",
pages = "155--160",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "2",

}

Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia : A report from the Taiwan Pediatric Oncology Group. / Liang, D. C.; Hung, I. J.; Yang, C. P.; Lin, K. H.; Chen, Chien-Hsu; Hsiao, T. C.; Chang, T. T.; Pui, C. H.; Lee, C. H.; Lin, K. S.

In: Leukemia, Vol. 13, No. 2, 01.01.1999, p. 155-160.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia

T2 - A report from the Taiwan Pediatric Oncology Group

AU - Liang, D. C.

AU - Hung, I. J.

AU - Yang, C. P.

AU - Lin, K. H.

AU - Chen, Chien-Hsu

AU - Hsiao, T. C.

AU - Chang, T. T.

AU - Pui, C. H.

AU - Lee, C. H.

AU - Lin, K. S.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count < 10 x 109/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count < 50 x 109/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1%, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide.

AB - The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count < 10 x 109/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count < 50 x 109/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1%, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide.

UR - http://www.scopus.com/inward/record.url?scp=0033000574&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033000574&partnerID=8YFLogxK

U2 - 10.1038/sj.leu.2401260

DO - 10.1038/sj.leu.2401260

M3 - Article

VL - 13

SP - 155

EP - 160

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 2

ER -