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

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.

• Authors: 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, P Dreger
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 52 Issue 4 Pg. 544-551 (Apr 2017) ISSN: 1476-5365 [Electronic] England
• PMID: 27941777 (Publication Type: Journal Article)

Chemical References

• Receptors, Antigen, T-Cell

Topics

• Adult
• Aged
• Clone Cells (immunology)
• Gene Rearrangement, T-Lymphocyte (genetics)
• Graft vs Leukemia Effect
• High-Throughput Nucleotide Sequencing
• Humans
• Immunomodulation
• Kinetics
• Leukemia, Prolymphocytic, T-Cell (diagnosis, therapy)
• Middle Aged
• Neoplasm, Residual (diagnosis, genetics)
• Real-Time Polymerase Chain Reaction
• Receptors, Antigen, T-Cell (analysis, genetics)
• Stem Cell Transplantation (methods)
• Transplantation, Homologous