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Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia

Rajala, Hanna L M; El Missiry, Mohamed; Ruusila, Anniina; Koskenvesa, Perttu; Brümmendorf, Tim H.; Gjertsen, Bjorn T.; Janssen, Jeroen Jwm; Lotfi, Kourosh; Markevärn, Berit and Olsson-Strömberg, Ulla, et al. (2017) In Journal of Cancer Research and Clinical Oncology 143(8). p.1543-1554
Abstract

Purpose: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. Methods: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. Results: Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of... (More)

Purpose: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. Methods: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. Results: Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of patients with IgA, IgG, and IgM levels below the lower limit of normal (LLN) was 0, 11, and 6% of all CML patients, respectively, whereas at 12 months timepoint the proportions were 6% (p = 0.13), 31% (p = 0.042) and 28% (p = 0.0078). Lower initial Ig levels predisposed to the development of hypogammaglobulinemia during TKI therapy. Decreased Ig levels in imatinib-treated patients were associated with higher percentages of immature BM B cells. The patients, who had low Ig levels during the TKI therapy, had significantly more frequent minor infections during the follow-up compared with the patients with normal Ig values (33% vs. 3%, p = 0.0016). No severe infections were reported, except recurrent upper respiratory tract infections in one imatinib-treated patient, who developed severe hypogammaglobulinemia. Conclusions: TKI treatment decreases plasma Ig levels, which should be measured in patients with recurrent infections.

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type
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publication status
published
subject
keywords
B cell, CML, Immunoglobulin, Tyrosine kinase inhibitor
in
Journal of Cancer Research and Clinical Oncology
volume
143
issue
8
pages
1543 - 1554
publisher
Springer
external identifiers
  • scopus:85015969804
ISSN
0171-5216
DOI
10.1007/s00432-017-2378-6
language
English
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no
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b9f7430f-68da-4be0-ac30-f23b598c94f5
date added to LUP
2017-05-03 17:17:04
date last changed
2018-07-01 04:45:10
@article{b9f7430f-68da-4be0-ac30-f23b598c94f5,
  abstract     = {<p>Purpose: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. Methods: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. Results: Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of patients with IgA, IgG, and IgM levels below the lower limit of normal (LLN) was 0, 11, and 6% of all CML patients, respectively, whereas at 12 months timepoint the proportions were 6% (p = 0.13), 31% (p = 0.042) and 28% (p = 0.0078). Lower initial Ig levels predisposed to the development of hypogammaglobulinemia during TKI therapy. Decreased Ig levels in imatinib-treated patients were associated with higher percentages of immature BM B cells. The patients, who had low Ig levels during the TKI therapy, had significantly more frequent minor infections during the follow-up compared with the patients with normal Ig values (33% vs. 3%, p = 0.0016). No severe infections were reported, except recurrent upper respiratory tract infections in one imatinib-treated patient, who developed severe hypogammaglobulinemia. Conclusions: TKI treatment decreases plasma Ig levels, which should be measured in patients with recurrent infections.</p>},
  author       = {Rajala, Hanna L M and El Missiry, Mohamed and Ruusila, Anniina and Koskenvesa, Perttu and Brümmendorf, Tim H. and Gjertsen, Bjorn T. and Janssen, Jeroen Jwm and Lotfi, Kourosh and Markevärn, Berit and Olsson-Strömberg, Ulla and Stenke, Leif and Stentoft, Jesper and Richter, Johan and Hjorth-Hansen, Henrik and Kreutzman, Anna and Mustjoki, Satu},
  issn         = {0171-5216},
  keyword      = {B cell,CML,Immunoglobulin,Tyrosine kinase inhibitor},
  language     = {eng},
  month        = {03},
  number       = {8},
  pages        = {1543--1554},
  publisher    = {Springer},
  series       = {Journal of Cancer Research and Clinical Oncology},
  title        = {Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia},
  url          = {http://dx.doi.org/10.1007/s00432-017-2378-6},
  volume       = {143},
  year         = {2017},
}