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

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.