title: Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.
abstract: The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.
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: Fabienne
authors.initials: F
authors.lastname: McClanahan
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Matthias
authors.initials: M
authors.lastname: Ritgen
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Fink
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Knauf
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Günter
authors.initials: G
authors.lastname: Brittinger
authors.forename: Manfred
authors.initials: M
authors.lastname: Hensel
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Andreas
authors.initials: A
authors.lastname: Bühler
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
mesh_terms: D000293:Adolescent; D000328:Adult; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous; D055815:Young Adult