title: Prognostic value of circulating Bcl-2/IgH levels in patients with follicular lymphoma receiving first-line immunochemotherapy.
abstract: Bcl-2/IgH rearrangements can be quantified in follicular lymphoma (FL) from peripheral blood (PB) by polymerase chain reaction (PCR). The prognostic value of Bcl-2/IgH levels in FL remains controversial. We therefore prospectively studied PB Bcl-2/IgH levels from 173 first-line FL patients who were consecutively enrolled, randomized, and treated within the multicenter phase 3 clinical trial NHL1-2003 comparing bendamustine-rituximab (B-R) with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone. From April 2005 to August 2008, 783 pre- and posttreatment PB samples were quantified by quantitative PCR. At inclusion, 114 patients (66%) tested positive and 59 (34%) were negative for Bcl-2/IgH. High pretreatment Bcl-2/IgH levels had an adverse effect on progression-free survival (PFS) compared with intermediate or low levels (high vs intermediate: hazard [HR], 4.28; 95% confidence interval [CI], 1.70-10.77; P = .002; high vs low: HR, 3.02; 95% CI, 1.55-5.86; P = .001). No PFS difference between treatment arms was observed in Bcl-2/IgH-positive patients. A positive posttreatment Bcl-2/IgH status was associated with shorter PFS (8.7 months vs not reached; HR, 3.15; 95% CI, 1.51-6.58; P = .002). By multivariate analysis, the pretreatment Bcl-2/IgH level was the strongest predictor for PFS. Our data suggest that pre- and posttreatment Bcl-2/IgH levels from PB have significant prognostic value for PFS in FL patients receiving first-line immunochemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT00991211 and at the German Federal Institute for Drugs and Medical Devices as #BfArM-4021335.
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Fabian
authors.initials: F
authors.lastname: Zohren
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Ingmar
authors.initials: I
authors.lastname: Bruns
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pechtel
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Roland
authors.initials: R
authors.lastname: Fenk
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Akos
authors.initials: A
authors.lastname: Czibere
authors.affiliation: Klinikum Ernst von Bergmann, Potsdam, Germany;
authors.forename: Georg
authors.initials: G
authors.lastname: Maschmeyer
authors.affiliation: Medizinische Hochschule Hannover, Hannover, Germany;
authors.forename: Dorothea
authors.initials: D
authors.lastname: Kofahl-Krause
authors.affiliation: Klinikum Leverkusen, Leverkusen, Germany;
authors.forename: Norbert
authors.initials: N
authors.lastname: Niederle
authors.affiliation: Kreiskrankenhaus Lüdenscheid, Lüdenscheid, Germany;
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heil
authors.affiliation: Onkologische Praxis Neuss, Neuss, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Losem
authors.affiliation: Onkologische Praxis Aschaffenburg, Aschaffenburg, Germany;
authors.forename: Manfred
authors.initials: M
authors.lastname: Welslau
authors.affiliation: Schwarzwald-Baar-Klinikum Villingen, Villingen, Germany; and.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Brugger
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
authors.affiliation: Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Barth
authors.affiliation: Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Mathias J
authors.initials: MJ
authors.lastname: Rummel
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.affiliation: University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany;
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000097:blood*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab / Q000008:administration & dosage / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: C582872:BCL2-IgH fusion protein, human; D015514:Oncogene Proteins, Fusion; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D011241:Prednisone