title: Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997.
abstract: Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL (#) . With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 vs. 48.1 months for F (n = 109) and FC (n = 118), respectively (p < 0.0001), and median overall survival (OS) was 88.0 vs. 79.1 months (p = 0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were age (p = 0.002, p < 0.001), Rai stage (p = 0.006, p = 0.02) and sex (p = 0.03, PFS only). Del(17)(p13.1) predicted shorter PFS and OS (p < 0.0001 for each), as did del(11q)(22.3) (p < 0.0001, p = 0.005, respectively), trisomy 12 with mutated Notch1 (p = 0.003, p = 0.03, respectively) and unmutated IGHV (p = 0.009, p = 0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL.
authors.affiliation: a Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lucas
authors.affiliation: a Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.affiliation: a Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lozanski
authors.affiliation: b Mayo Clinic , Rochester , MN , USA.
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.affiliation: a Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: Arletta
authors.initials: A
authors.lastname: Lozanski
authors.affiliation: c University of Freiburg Medical Center , Freiburg , Germany.|d German Cancer Research Center , Heidelberg , Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Claus
authors.affiliation: d German Cancer Research Center , Heidelberg , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.affiliation: e Sarah Cannon Research Institute and Tennessee Oncology , Nashville , TN , USA.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.affiliation: f Dana Farber Cancer Institute , Boston , MA , USA.
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.affiliation: g Montefiore Medical Center , Bronx , NY , USA.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Paietta
authors.affiliation: h University of Rochester , Rochester , NY , USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.affiliation: b Mayo Clinic , Rochester , MN , USA.
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.affiliation: i Barts Cancer Institute, Queen Mary University of London , London , UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.affiliation: j Celgene Corporation , Summit , NJ , USA.
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Hussein
authors.affiliation: k Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: l University of Chicago , Chicago , IL , USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.affiliation: m Cancer Center of Kansas , Wichita , KS , USA.
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Moore
authors.affiliation: n Memorial Sloan Kettering Cancer Center , New York , NY , USA.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: a Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: a Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D002869:Chromosome Aberrations; D018899:CpG Islands; D003520:Cyclophosphamide / Q000008:administration & dosage; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; D003520:Cyclophosphamide; D051746:ZAP-70 Protein-Tyrosine Kinase; D014740:Vidarabine; C024352:fludarabine
keywords: Fludarabine; chemotherapy; chronic lymphocytic leukemia; cyclophosphamide