Publication details
GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Bone Marrow Transplantation |
| MU Faculty or unit | |
| 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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