title: Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP.
abstract: We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Including International Prognostic Index (IPI) as a variable in a penalized Cox regression, we investigated the association with disease progression for single genes or gene combinations in four models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B. This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P < 0·001). However, a simpler, IPI independent model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs. 82% for low risk group (P < 0·001). We have documented the impact of a few single genes added to IPI for assignment in new drug trials.
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Green
authors.affiliation: Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Jensen
authors.affiliation: Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Holst
authors.affiliation: Department of Haematology, Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Falgreen
authors.affiliation: Department of Haematology, Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Bøgsted
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Karin
authors.initials: K
authors.lastname: de Stricker
authors.affiliation: Department of Haematology, Vejle Hospital, Vejle, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.affiliation: Department of Haematology, Sydvestjysk Hospital, Esbjerg, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Mourits-Andersen
authors.affiliation: Department of Haematology, Hospital of Southern Denmark, Aabenraa, Denmark.
authors.forename: Mikael
authors.initials: M
authors.lastname: Frederiksen
authors.affiliation: Department of Haematology, Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Johnsen
authors.affiliation: Department of Haematology, Roskilde Hospital, Roskilde, Denmark.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Pedersen
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Møller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001706:Biopsy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: R-CHOP; biomarker; diffuse large B-cell lymphoma; prognostic model; statistical methodology