Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia:: results from the GCLLSG CLL3X trial

The purpose of this study was to prospectively analyze minimal residual disease (MRD) kinetics after reduced-intensity allogeneic stem cell transplantation (allo-SCT) in high-risk chronic lymphocytic leukemia (CLL). Subjects were the first 30 consecutive patients from a prospective clinical trial, and seven pilot patients treated identically. Using real-time quantitativePCR (RQ-PCR) and/or flow-based MRD monitoring (sensitivity >= 10(-4)), five distinct patterns of MRD kinetics could be identified: patients who promptly achieved durable MRD negativity without direct evidence of graft- versus-leukemia (GVL) effects (Group 1) (n = 4; no clinical relapse); patients with complete and sustained MRD response after GVL induced by immunosuppression tapering (Group 2) or donor lymphocyte infusions (Group 3) (n = 18; one relapse); patients without MRD response due to lack of GVL (Group 4) (n = 2; two relapses); patients with incomplete and transient MRD response to GVL (Group 5) (n = 4; three relapses). In summary, this study provides a comprehensive map of possible MRD courses and their prognostic implications after T-replete allo-SCT in high-risk CLL, indicating that effective GVL activity is induced virtually in all patients who develop chronic GVHD. However, in a significant proportion of cases, this does not translate into sustained disease control due to development of secondary GVL resistance.