title: 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.
abstract: 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.
authors.affiliation: Department of Medicine V, University of Heidelberg, Heidelberg, Germany. peter.dreger@med.uni-heidelberg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Matthias
authors.initials: M
authors.lastname: Ritgen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böttcher
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Sascha
authors.initials: S
authors.lastname: Dietrich
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Sandra
authors.initials: S
authors.lastname: Cohen
authors.forename: Jörg
authors.initials: J
authors.lastname: Schubert
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Dietrich
authors.initials: D
authors.lastname: Beelen
authors.forename: Matthias
authors.initials: M
authors.lastname: Zeis
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Justin
authors.initials: J
authors.lastname: Hasenkamp
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
authors.forename: Andreas
authors.initials: A
authors.lastname: Humpe
authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
mesh_terms: 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