Journal
LEUKEMIA
Volume 22, Issue 4, Pages 783-790Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2405104
Keywords
acute myeloid leukemia; chronic myeloid leukemia; myelodysplastic syndrome; GM-CSF; autoantibodies
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Funding
- NCI NIH HHS [CA100271, R01 CA081247, CA81247] Funding Source: Medline
- PHS HHS [C49639] Funding Source: Medline
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Antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can be induced when GM-CSF is used as an adjuvant to solid tumor vaccination. Neutralizing anti-GM-CSF IgG has been associated with pulmonary alveolar proteinosis ( PAP), and secondary PAP has been linked to myeloid leukemia. We studied 69 patients with acute myeloid leukemia, chronic myeloid leukemia and myelodysplastic syndrome, including 19 patients who received GM-CSF with peptide antigen and incomplete Freund's adjuvant in a vaccine trial for the presence or induction of anti-GM-CSF antibodies. Anti-GM-CSF IgG were present in 36 (52%) patients with myeloid leukemia compared to only 1 of 33 (3%) healthy subjects (P = 0.008) and in none of 6 patients with lymphoid leukemia (P = 0.0001). Antibody titers were unaffected by vaccination. Anti-GM-CSF IgA and IgM were found in 33 and 20% of patients, respectively; IgA from two patients neutralized GM-CSF. Strikingly, while anti-GM-CSF IgG titers were higher in patients with active disease (n = 52) versus those in complete remission (n = 14, P = 0.0009), GM-CSF expression was not increased in either group. These data are first to show that anti-GM-CSF antibodies of multiple isotypes are present in patients with active myeloid leukemia without PAP and may be useful markers of disease activity.
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