title: 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.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: L
authors.identifier: http://orcid.org/0000-0002-7893-401X
authors.initials: L
authors.lastname: Sellner
authors.affiliation: Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brüggemann
authors.affiliation: Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schlitt
authors.affiliation: Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Knecht
authors.affiliation: Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Herrmann
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Reigl
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Krejci
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Bystry
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: N
authors.initials: N
authors.lastname: Darzentas
authors.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.|Oncology Practice Darmstadt, Darmstadt, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rieger
authors.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.|Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dietrich
authors.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Luft
authors.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kneba
authors.affiliation: Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dreger
mesh_terms: D000328:Adult; D000368:Aged; D002999:Clone Cells / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D020544:Graft vs Leukemia Effect; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056747:Immunomodulation; D007700:Kinetics; D015461:Leukemia, Prolymphocytic, T-Cell / Q000175:diagnosis / Q000628:therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics; D033581:Stem Cell Transplantation / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D011948:Receptors, Antigen, T-Cell