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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5509-5514.
Prepublished online as a Blood First Edition Paper on April 29, 2008; DOI 10.1182/blood-2008-02-136374.
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Submitted February 4, 2008
Accepted April 6, 2008
Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP
Raquel Malumbres, Jun Chen, Rob Tibshirani, Nathalie A Johnson, Laurie H Sehn, Yaso Natkunam, Javier Briones, Ranjana Advani, Joseph M Connors, Gerald E Byrne, Ronald Levy, Randy D Gascoyne, and Izidore S Lossos*
Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, University of Miami, Miami, FL, United States
Department of Health Research and Policy and Statistics, Stanford University, Stanford, CA, United States
Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada
Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada
Department of Pathology, Stanford University, Stanford, CA, United States
Department of Clinical Hematology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, United States
Department of Pathology, University of Maimi, Miami, FL, United States
* Corresponding author; email: ilossos{at}med.miami.edu.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by variable clinical outcomes. Outcome prediction at the time of diagnosis is of paramount importance. Previously, we constructed a 6-gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies (Lossos et al NEJM 2004, 350:1829). However, the standard therapy has evolved into rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Herein, we evaluated the predictive power of a paraffin-based 6-gene model in R-CHOP treated DLBCL patients. RNA was successfully extracted from 132 formalin-fixed paraffin-embedded (FFPE) specimens. Expression of the 6 genes comprising the model was measured and the mortality predictor score was calculated for each patient. The mortality predictor score divided patients into low-risk (below median) and high-risk (above median) subgroups with significantly different overall survival (OS) (p=0.0021) and progression-free survival (PFS) (p=0.038). The model also predicted OS and PFS when the mortality predictor score was considered as a continuous variable (p=0.0022 and 0.0098, respectively) and was independent of the IPI for prediction of OS (P=0.0083). These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE tissue from initial diagnostic biopsies.
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