Journal
BONE MARROW TRANSPLANTATION
Volume 52, Issue 4, Pages 544-551Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2016.305
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Funding
- CEITEC MU [CZ.1.05/1.1.00/02.0068]
- EuroClonality
- MetaCentrum [LM2010005]
- 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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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 nextgeneration 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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