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Chronic Leukemia

GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses

Bone Marrow Transplantation volume 52, pages 544–551 (2017)Cite this article

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A Corrigendum to this article was published on 05 April 2017

This article has been updated

Abstract

Allogeneic stem cell transplantation (alloSCT) is used for treating patients with T-prolymphocytic leukemia (T-PLL). However, direct evidence of GvL activity in T-PLL is lacking. We correlated minimal residual disease (MRD) kinetics with immune interventions and T-cell receptor (TCR) repertoire diversity alterations in patients after alloSCT for T-PLL. Longitudinal quantitative MRD monitoring was performed by clone-specific real-time PCR of TCR rearrangements (n=7), and TCR repertoire diversity assessment by next-generation sequencing (NGS; n=3) Although post-transplant immunomodulation (immunosuppression tapering or donor lymphocyte infusions) resulted in significant reduction (>1 log) of MRD levels in 7 of 10 occasions, durable MRD clearance was observed in only two patients. In all three patients analyzed by TCR-NGS, MRD responses were reproducibly associated with a shift from a clonal, T-PLL-driven profile to a polyclonal signature. Novel clonotypes that could explain a clonal GvL effect did not emerge. In conclusion, TCR-based MRD quantification appears to be a suitable tool for monitoring and guiding treatment interventions in T-PLL. The MRD responses to immune modulation observed here provide first molecular evidence for GvL activity in T-PLL which, however, may be often only transient and reliant on a poly-/oligoclonal rather than a monoclonal T-cell response.

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  • 05 April 2017

    This article has been corrected since Advance Online Publication and a corrigendum is also printed in this issue.

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Acknowledgements

We thank all our patients for their kind willingness to contribute clinical data and biological samples to make this study possible. TR, AK, VB, ND funded by CEITEC MU (CZ.1.05/1.1.00/02.0068) and EuroClonality, with computational resources provided by MetaCentrum under program LM2010005, and CERIT-SC under program Centre CERIT Scientific Cloud, part of the Operational Program Research and Development for Innovations, CZ.1.05/3.2.00/08.0144.

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Authors and Affiliations

  1. Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany

    L Sellner, M Rieger, S Dietrich, T Luft, A D Ho & P Dreger

  2. Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany

    M Brüggemann, M Schlitt, H Knecht, D Herrmann & M Kneba

  3. Central European Institute of Technology, Masaryk University, Brno, Czech Republic,

    T Reigl, A Krejci, V Bystry & N Darzentas

  4. Oncology Practice Darmstadt, Darmstadt, Germany

    M Rieger

  5. Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany

    S Dietrich

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  1. L Sellner
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Correspondence to L Sellner.

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Additional information

Presented in part in abstract form at the 57th Annual Meeting of the American Society of Hematology (ASH; December 5–8, 2015, Orlando, FL, USA) and the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT; April 3–6, 2016, Valencia, Spain).

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Sellner, L., Brüggemann, M., Schlitt, M. et al. GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses. Bone Marrow Transplant 52, 544–551 (2017). https://doi.org/10.1038/bmt.2016.305

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