The majority of children and adolescents with acute myeloid leukemia have detectable anti-DT388-GMCSF IgG concentrations, but at concentrations that should not preclude in vivo activity

Philip D. Hall, Bassem I. Razzouk, Tony E. Willoughby, Thomas W. McLean, Arthur E. Frankel

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Purpose: As a novel approach for the treatment of acute myeloid leukemia (AML), the authors are developing a fusion toxin (DT388-GMCSF) consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor (GMCSF). A critical step in the development of DT388-GMCSF for clinical use in childhood and adolescent AML is to determine whether children and adolescents have preexisting antibodies to DT388-GMCSF due to childhood immunizations against diphtheria toxoid. Patients and Methods: Sera from 33 children and adolescents with AML and one with juvenile myelomonocytic leukemia were collected. The median age was 11.8 years. All scheduled diphtheria toxoid vaccinations were current except for the child diagnosed at 4 months of age. Anti-DT388-GMCSF antibody concentrations were detected by an enzymoimmunoassay and by an in vitro bioassay. Results: Thirty of 34 (88%) children and adolescents had detectable anti-DT388-GMCSF IgG antibody concentrations, The median concentration was 1.5 μg/mL, with a range from undetectable to 191.4 μg/mL. There was a positive correlation between the enzymoimmunoassay and bioassay. There was no difference between the anti-DT388-GMCSF IgG concentrations in these children and adolescents with AML and in 43 adults with AML. Preliminary results of the phase 1 trial of DT388-GMCSF in adults with AML indicate that patients with baseline anti-DT388-GMCSF IgG concentrations of less than 2 μg/mL can achieve circulating DT388-GMCSF concentrations and can exhibit antileukemic activity. Twenty-three of 34 (67.6%) children and adolescents had anti-DT388-GMCSF IgG concentrations less than 2 μg/mL. Conclusions: Despite routine diphtheria toxoid vaccinations, most children and adolescents with AML do not have anti-DT388-GMCSF IgG concentrations that preclude in vivo activity of DT388-GMCSF.

Original languageEnglish (US)
Pages (from-to)521-526
Number of pages6
JournalJournal of Pediatric Hematology/Oncology
Volume24
Issue number7
DOIs
StatePublished - Oct 1 2002

Keywords

  • Acute myeloid leukemia
  • Diphtheria fusion toxin
  • Human GM-CSF

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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