title: Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial.
abstract: 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 quantitative-PCR (RQ-PCR) and/or flow-based MRD monitoring (sensitivity >or=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.
authors.affiliation: Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ritgen
authors.forename: S
authors.initials: S
authors.lastname: Böttcher
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: D
authors.initials: D
authors.lastname: Bunjes
authors.forename: J
authors.initials: J
authors.lastname: Schubert
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Humpe
authors.forename: M
authors.initials: M
authors.lastname: Hallek
authors.forename: M
authors.initials: M
authors.lastname: Kneba
authors.forename: N
authors.initials: N
authors.lastname: Schmitz
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: P
authors.initials: P
authors.lastname: Dreger
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D014184:Transplantation, Homologous