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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy

Authors: Meghali Goswami, Gabrielle Prince, Angelique Biancotto, Susan Moir, Lela Kardava, Brian H. Santich, Foo Cheung, Yuri Kotliarov, Jinguo Chen, Rongye Shi, Huizhi Zhou, Hana Golding, Jody Manischewitz, Lisa King, Lauren M. Kunz, Kimberly Noonan, Ivan M. Borrello, B. Douglas Smith, Christopher S. Hourigan

Published in: Journal of Translational Medicine | Issue 1/2017

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Abstract

Background

Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy.

Methods

We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets.

Results

Only 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy.

Conclusion

Our results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. 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.
Appendix
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Metadata
Title
Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy
Authors
Meghali Goswami
Gabrielle Prince
Angelique Biancotto
Susan Moir
Lela Kardava
Brian H. Santich
Foo Cheung
Yuri Kotliarov
Jinguo Chen
Rongye Shi
Huizhi Zhou
Hana Golding
Jody Manischewitz
Lisa King
Lauren M. Kunz
Kimberly Noonan
Ivan M. Borrello
B. Douglas Smith
Christopher S. Hourigan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1252-2

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