title: Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR.
abstract: The aim of this study was to investigate if graft-versus-leukemia (GVL) activity conferred by allogeneic stem cell transplantation (allo-SCT) is effective in chronic lymphocytic leukemia (CLL) with unmutated V(H) gene status. The kinetics of residual disease (MRD) were measured by quantitative allele-specific immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) in 9 patients after nonmyeloablative allo-SCT for unmutated CLL. Despite an only modest decrease in the early posttransplantation phase, MRD became undetectable in 7 of 9 patients (78%) from day +100 onwards subsequent to chronic graft-versus-host disease or donor lymphocyte infusions. With a median follow-up of 25 months (range, 14-37 months), these 7 patients remain in continuous clinical and molecular remission. In contrast, PCR negativity was achieved in only 6 of 26 control patients (23%) after autologous SCT for unmutated CLL and it was not durable. Taken together, this study shows for the first time that GVL-mediated immunotherapy might be effective in CLL with unmutated V(H).
authors.affiliation: Second Department of Internal Medicine, Chemnitzstr 33, D-24116 Kiel, Germany. m.ritgen@med2.uni-kiel.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Ritgen
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Andreas
authors.initials: A
authors.lastname: Humpe
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Thorsten
authors.initials: T
authors.lastname: Raff
authors.forename: Alexander
authors.initials: A
authors.lastname: Kröber
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Richard
authors.initials: R
authors.lastname: Schlenk
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
mesh_terms: D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods*; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains