GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses
GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
Bone marrow transplantation
Year: 2016, Volume: 52, Issue: 4, Pages: 544-551 |
| ISSN: | 1476-5365 |
| DOI: | 10.1038/bmt.2016.305 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/bmt.2016.305 Verlag, Volltext: https://www.nature.com/articles/bmt2016305 
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| Author Notes: | L. Sellner, M. Brüggemann, M. Schlitt, H. Knecht, D. Herrmann, T. Reigl, A. Krejci, V. Bystry, N. Darzentas, M. Rieger, S. Dietrich, T. Luft, A. D. Ho, M. Kneba and P. Dreger |
| Summary: | GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses 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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| Item Description: | Published online: 12 December 2016 Gesehen am 04.07.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5365 |
| DOI: | 10.1038/bmt.2016.305 |