Abstract
In a phase IV trial, eighty-four patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin-2 (IL-2) to prevent relapse in the post-consolidation phase. Aspects of natural killer (NK) cell biology were analyzed before and during immunotherapy with focus on outcome in older patients. In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56(bright) and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. In older patients, a high expression of NKp30 or NKp46 on CD16+ NK cells before and during therapy predicted leukemia-free and overall survival. These results suggest that NK cell functions determine relapse risk and survival in older AML patients and point to biomarkers of efficacy in protocols for remission maintenance.
Keywords:
Immune response; Immunity; Immunology and Microbiology Section; NKp30; NKp46; acute myeloid leukemia; immunotherapy; natural killer cells.
Publication types
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Clinical Trial, Phase IV
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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CD56 Antigen / biosynthesis
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CD56 Antigen / immunology
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Female
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Flow Cytometry
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GPI-Linked Proteins / biosynthesis
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GPI-Linked Proteins / immunology
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Histamine / administration & dosage
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Humans
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Immunotherapy / methods*
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Interleukin-2 / administration & dosage
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Interleukin-2 / analogs & derivatives
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Kaplan-Meier Estimate
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Killer Cells, Natural / immunology*
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Leukemia, Myeloid, Acute / immunology*
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Leukemia, Myeloid, Acute / mortality
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Leukemia, Myeloid, Acute / therapy
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Lymphocyte Subsets / immunology*
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Maintenance Chemotherapy / methods
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Male
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Middle Aged
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Natural Cytotoxicity Triggering Receptor 1 / biosynthesis
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Natural Cytotoxicity Triggering Receptor 1 / immunology
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Natural Cytotoxicity Triggering Receptor 3 / biosynthesis
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Natural Cytotoxicity Triggering Receptor 3 / immunology
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Neoplasm Recurrence, Local / immunology
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Receptors, IgG / biosynthesis
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Receptors, IgG / immunology
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Recombinant Proteins / administration & dosage
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Remission Induction
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Young Adult
Substances
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CD56 Antigen
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FCGR3B protein, human
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GPI-Linked Proteins
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Interleukin-2
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NCAM1 protein, human
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NCR1 protein, human
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NCR3 protein, human
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Natural Cytotoxicity Triggering Receptor 1
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Natural Cytotoxicity Triggering Receptor 3
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Receptors, IgG
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Recombinant Proteins
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Histamine
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aldesleukin