Initial chemotherapy often alters B-cell composition and immunity in patients with acute myeloid leukemia (AML), which may have implications for the success of further immunotherapy, according to research published in Journal of Translational Medicine (published online July 10, 2017; doi:10.1186/s12967-017-1252-2).
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Initial and intensive cytotoxic chemotherapy often alters the B-cell composition and humoral immunity of adult patients with AML. Though immunotherapeutic strategies to continue remission after intensive chemotherapy are being tested in clinical trials, there is an incomplete description of the state of the adaptive immune system in patients with AML who have completed chemotherapy.
Meghali Goswami, BS, National Institutes of Health, and colleagues conducted a study to assess the functional capacity of the immune system in adult patients with AML who have completed initial chemotherapy and are candidates for immunotherapy. Researchers sampled 10 patients (median age, 57 years) with AML who were in complete remission after chemotherapy. Patients demonstrated genetic, phenotypic, and functional characteristics of adaptive immune cell subsets. Ten additional healthy control patients were recruited for B-cell and T-cell comparisons.
Patients were given the seasonal influenza vaccination and blood samples were taken on the day of vaccination and 30 days post-vaccination. Response to the vaccination was used as a surrogate for the robustness of their immune systems.
A majority of patients exhibited abnormal frequencies of translational and memory B-cells after the influenza vaccination. Only two patients (20%) demonstrated protective titers in response to the vaccination. B-cell receptor sequencing showed a B-cell repertoire with limited evidence of somatic hypermutation in a majority of patients.
Interestingly, T-cell population levels were similar to those seen in patients not receiving the vaccination. Cytotoxic T-cells demonstrated antigen-specific activity after the vaccination, researcher wrote. PD-1 expression was increased in the T-cells of patients with AML least removed from chemotherapy.
Researchers concluded that while cellular immunity may recover quickly, humoral immunity is incompletely recovered within the year following intensive cytotoxic chemotherapy in adult patients with AML. B-cell abnormalities may explain why poor responses are seen after influenza vaccination for these patients.
“Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy,” they concluded. A further understanding of changes in the adaptive immune system for patients with AML after chemotherapy will be helpful in designing more effective immunotherapies.—Zachary Bessette
