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

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Authors	SELLNER L. BRUGGEMANN M. SCHLITT M. KNECHT H. HERRMANN D. REIGL Tomáš KREJČÍ Adam BYSTRÝ Vojtěch DARZENTAS Nikos RIEGER M. DIETRICH S. LUFT T. HO A.D. KNEBA M. DREGER P.
Year of publication	2017
Type	Article in Periodical
Magazine / Source	Bone Marrow Transplantation
MU Faculty or unit	Central European Institute of Technology
Citation
Web	https://www.nature.com/articles/bmt2016305
Doi	http://dx.doi.org/10.1038/bmt.2016.305
Keywords	STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MARROW TRANSPLANTATION; CLINICAL-SIGNIFICANCE; GENE REARRANGEMENTS; ADULT PATIENTS; STANDARD-RISK; CLL3X TRIAL
Description	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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