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Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia
Univ Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.;Helsinki Univ Hosp, Ctr Comprehens Canc, Haartmaninkatu 8, Helsinki 00290, Finland..
Univ Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.;Helsinki Univ Hosp, Ctr Comprehens Canc, Haartmaninkatu 8, Helsinki 00290, Finland..
Univ Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.;Helsinki Univ Hosp, Ctr Comprehens Canc, Haartmaninkatu 8, Helsinki 00290, Finland..
Univ Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Haartmaninkatu 8, FIN-00290 Helsinki, Finland.;Helsinki Univ Hosp, Ctr Comprehens Canc, Haartmaninkatu 8, Helsinki 00290, Finland..
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2017 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 143, no 8, p. 1543-1554Article in journal (Refereed) Published
Abstract [en]

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 imatinibtreated 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.

Place, publisher, year, edition, pages
SPRINGER , 2017. Vol. 143, no 8, p. 1543-1554
Keywords [en]
CML, Tyrosine kinase inhibitor, B cell, Immunoglobulin
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-329902DOI: 10.1007/s00432-017-2378-6ISI: 000405312900015OAI: oai:DiVA.org:uu-329902DiVA, id: diva2:1184253
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-02-20Bibliographically approved

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Stromberg, Ulla Ohlsson

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