Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.
The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.
Dreger
Peter
P
Department of Medicine V, University of Heidelberg, Heidelberg, Germany. peter.dreger@med.uni-heidelberg.de
Döhner
Hartmut
H
Ritgen
Matthias
M
Böttcher
Sebastian
S
Busch
Raymonde
R
Dietrich
Sascha
S
Bunjes
Donald
D
Cohen
Sandra
S
Schubert
Jörg
J
Hegenbart
Ute
U
Beelen
Dietrich
D
Zeis
Matthias
M
Stadler
Michael
M
Hasenkamp
Justin
J
Uharek
Lutz
L
Scheid
Christof
C
Humpe
Andreas
A
Zenz
Thorsten
T
Winkler
Dirk
D
Hallek
Michael
M
Kneba
Michael
M
Schmitz
Norbert
N
Stilgenbauer
Stephan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D016678:Genome; D005858:Germany; D006086:Graft vs Host Disease / Q000473:pathology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery* / Q000628:therapy; D017710:Lymphocyte Transfusion; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics / Q000601:surgery / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome