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.
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).
Ritgen
Matthias
M
Second Department of Internal Medicine, Chemnitzstr 33, D-24116 Kiel, Germany. m.ritgen@med2.uni-kiel.de
Stilgenbauer
Stephan
S
von Neuhoff
Nils
N
Humpe
Andreas
A
Brüggemann
Monika
M
Pott
Christiane
C
Raff
Thorsten
T
Kröber
Alexander
A
Bunjes
Donald
D
Schlenk
Richard
R
Schmitz
Norbert
N
Döhner
Hartmut
H
Kneba
Michael
M
Dreger
Peter
P
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
D007143:Immunoglobulin Heavy Chains