Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia

A children's oncology group report

Richard H. Ko, Tamekia Jones, David Radvinsky, Nathan Robison, Paul S. Gaynon, Eduard H. Panosyan, Ioannis A. Avramis, Vassilios I. Avramis, Joan Rubin, Lawrence J. Ettinger, Nita L. Seibel, Girish Dhall

Research output: Contribution to journalArticle

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Abstract

BACKGROUND The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. METHODS Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. RESULTS During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P <.0001) or PEG ASNase (odds ratio, 3.08; P <.0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P =.66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P <.001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P =.68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P =.22) were significantly different. CONCLUSIONS The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.

Original languageEnglish (US)
Pages (from-to)4205-4211
Number of pages7
JournalCancer
Volume121
Issue number23
DOIs
StatePublished - Dec 1 2015

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hypersensitivity
Antibodies
Erwinia
Disease-Free Survival
Odds Ratio
Anti-Idiotypic Antibodies
Pectobacterium chrysanthemi
Incidence
Survival Rate
Maintenance
Escherichia coli
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia : A children's oncology group report. / Ko, Richard H.; Jones, Tamekia; Radvinsky, David; Robison, Nathan; Gaynon, Paul S.; Panosyan, Eduard H.; Avramis, Ioannis A.; Avramis, Vassilios I.; Rubin, Joan; Ettinger, Lawrence J.; Seibel, Nita L.; Dhall, Girish.

In: Cancer, Vol. 121, No. 23, 01.12.2015, p. 4205-4211.

Research output: Contribution to journalArticle

Ko, RH, Jones, T, Radvinsky, D, Robison, N, Gaynon, PS, Panosyan, EH, Avramis, IA, Avramis, VI, Rubin, J, Ettinger, LJ, Seibel, NL & Dhall, G 2015, 'Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia: A children's oncology group report', Cancer, vol. 121, no. 23, pp. 4205-4211. https://doi.org/10.1002/cncr.29641
Ko, Richard H. ; Jones, Tamekia ; Radvinsky, David ; Robison, Nathan ; Gaynon, Paul S. ; Panosyan, Eduard H. ; Avramis, Ioannis A. ; Avramis, Vassilios I. ; Rubin, Joan ; Ettinger, Lawrence J. ; Seibel, Nita L. ; Dhall, Girish. / Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia : A children's oncology group report. In: Cancer. 2015 ; Vol. 121, No. 23. pp. 4205-4211.
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title = "Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia: A children's oncology group report",
abstract = "BACKGROUND The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. METHODS Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. RESULTS During the consolidation phase, 289 of 990 patients (29.2{\%}) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P <.0001) or PEG ASNase (odds ratio, 3.08; P <.0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8{\%} ± 2.8{\%} and 81.6{\%} ± 3.8{\%}, respectively; P =.66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P <.001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80{\%} ± 2.6{\%} and 77.7{\%} ± 4.3{\%}, respectively; P =.68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P =.22) were significantly different. CONCLUSIONS The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.",
author = "Ko, {Richard H.} and Tamekia Jones and David Radvinsky and Nathan Robison and Gaynon, {Paul S.} and Panosyan, {Eduard H.} and Avramis, {Ioannis A.} and Avramis, {Vassilios I.} and Joan Rubin and Ettinger, {Lawrence J.} and Seibel, {Nita L.} and Girish Dhall",
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T1 - Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia

T2 - A children's oncology group report

AU - Ko, Richard H.

AU - Jones, Tamekia

AU - Radvinsky, David

AU - Robison, Nathan

AU - Gaynon, Paul S.

AU - Panosyan, Eduard H.

AU - Avramis, Ioannis A.

AU - Avramis, Vassilios I.

AU - Rubin, Joan

AU - Ettinger, Lawrence J.

AU - Seibel, Nita L.

AU - Dhall, Girish

PY - 2015/12/1

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N2 - BACKGROUND The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. METHODS Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. RESULTS During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P <.0001) or PEG ASNase (odds ratio, 3.08; P <.0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P =.66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P <.001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P =.68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P =.22) were significantly different. CONCLUSIONS The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.

AB - BACKGROUND The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. METHODS Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. RESULTS During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P <.0001) or PEG ASNase (odds ratio, 3.08; P <.0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P =.66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P <.001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P =.68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P =.22) were significantly different. CONCLUSIONS The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.

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