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Chronic myelogenous leukemia

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML

Leukemia volume 31, pages 829–836 (2017)Cite this article

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A Corrigendum to this article was published on 30 January 2018

Abstract

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86+pDC frequencies than normal donors (P<0.0024), whereas TFR patients had consistently low CD86+pDC (n=12). This suggested that low CD86+pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6–47.9) for patients with >95 CD86+pDC per 105 lymphocytes, but 70.0% (95% CI 59.3–78.3) for patients with <95 CD86+pDC (hazard ratio (HR) 3.4, 95%-CI: 1.9–6.0; P<0.0001). Moreover, only patients with <95 CD86+pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1–0.8; P=0.0263). High CD86+pDC counts significantly correlated with leukemia-specific CD8+ T-cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21–0.92; P=0.0098). Our data demonstrate that CML patients with high CD86+pDC counts have a higher risk of relapse after TKI discontinuation.

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Acknowledgements

This work was supported by the Clinical Research Group - KFO210 - of the German Research Foundation (DFG), and by the German José Carreras Leukaemia Foundation (DJCLS, R14/07 and AH 06-01).

Author contributions

AB designed the study, recruited and treated patients, interpreted the data and wrote the manuscript. CS processed samples, acquired the analytical data, analyzed the results, and helped generating figures and writing the manuscript. MP did the statistical analysis, interpreted the data, generated figures and helped in writing the manuscript. JG acquired and processed the clinical data and contributed to the statistical analysis. FF contributed to the statistical analysis. SS and FXM were the principal investigators of the EURO-SKI trial, SS recruited and treated patients of this sub-study. MM, EE, THB, CW, JD, MEG, RH, GF, SH, TI, YW, TL, AH recruited and treated patients. SI, CTD, CAB, YW, MH, RH, AN were involved in data acquisition and interpretation. All authors interpreted the data, drafted and reviewed the report, gave their final approval for publication, and agreed to be accountable for all aspects of the work.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany

    C Schütz, S Inselmann, C A Brendel, S K Metzelder, Y Wang, A Neubauer & A Burchert

  2. III. Medizinische Klinik, Medizinische Fakultät Mannheim, University Heidelberg, Mannheim, Germany

    S Sausslele, C T Dietz, M C Müller & R Hehlmann

  3. Department of Hematology and Oncology, University Hospital Jena, Jena, Germany

    E Eigendorff & A Hochhaus

  4. Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, RWTH Aachen University Hospital, Aachen, Germany

    T H Brümmendorf

  5. Department of Hematology and Oncology, University Hospital Freiburg,

    C Waller

  6. Onkologische Praxis Heilbronn, Heilbronn, Germany

    J Dengler

  7. Department of Hematology and Oncology, University Hospital Würzburg, Würzburg, Germany

    M E Goebeler

  8. Department of Hematology/Oncology, Klinikum Chemnitz, Chemnitz, Germany

    R Herbst

  9. MVZ Klinikum Straubing GmbH, Straubing, Germany

    G Freunek

  10. Klinikum Kempten-Oberallgäu GmbH, Kempten, Germany

    S Hanzel

  11. BAG Freiberg-Richter, Jacobasch, Wolf, Illmer, Dresden, Germany

    T Illmer

  12. Asklepios Klinikum Weißenfels, Weißenfels, Germany

    T Lange

  13. Center for Tumor and Immunbiology, University Marburg, Marburg, Germany

    F Finkernagel

  14. Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Biomedical Research Center (BMFZ), Marburg, Germany

    M Huber

  15. Clinical Investigation Center, Poitiers, France

    J Guilhot

  16. Hematology Laboratory, CHU Bordeaux, Bordeaux, France

    F Xavier Mahon

  17. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, Munich, Germany

    M Pfirrmann

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  1. C Schütz
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AB reports personal fees from Bristol-Myers Squibb, outside the submitted work. SS, AH, FXM, MM report honoraria, travel support and research support from Novartis, Bristol-Myers Squibb, Ariad and Pfizer, outside the submitted work.

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Schütz, C., Inselmann, S., Sausslele, S. et al. Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML. Leukemia 31, 829–836 (2017). https://doi.org/10.1038/leu.2017.9

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