BACKGROUND: High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab (R)-era' are lacking. METHODS: To test reproducibility and applicability of observations from the 'pre-R era' to the 'R era', we examined the prognostic role of CCNE expression by immunohistochemistry in 1579 DLBCL on tissue microarrays (TMA); 339 patients were treated by CHOP and 635 by R-CHOP. RESULTS: 1209 samples (77%) were evaluable; failures were due to missing TMA punches and fixation artefacts. Mean expression of CCNE was 13% (0-85%); applying a cut-off of >16%, 382 DLBCL (31%) were positive. CCNE did not correlate with any of the known variables (IPI, primary site, cell of origin, proliferation, and BCL2- or C-MYC rearrangements). We were able to reproduce data suggesting an IPI- and response to therapy independent, negative prognostic impact of CCNE in CHOP-treated DLBCL patients: CCNE-positive cases had a median survival of 16 months compared with 57 months in negative ones (p=0.012). In R-CHOP-treated patients the prognostic impact of CCNE was abrogated and only IPI, cell of origin and response to therapy had a prognostic significance. CONCLUSIONS: Addition of R to CHOP overcomes the negative prognostic impact of CCNE in DLBCL. Thus, R not only prolongs survival in DLBCL but also serves a cautionary note that prognostic factors should not be transferred into the 'R era' without proper scientific studies.
BACKGROUND: High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab (R)-era' are lacking. METHODS: To test reproducibility and applicability of observations from the 'pre-R era' to the 'R era', we examined the prognostic role of CCNE expression by immunohistochemistry in 1579 DLBCL on tissue microarrays (TMA); 339 patients were treated by CHOP and 635 by R-CHOP. RESULTS: 1209 samples (77%) were evaluable; failures were due to missing TMA punches and fixation artefacts. Mean expression of CCNE was 13% (0-85%); applying a cut-off of >16%, 382 DLBCL (31%) were positive. CCNE did not correlate with any of the known variables (IPI, primary site, cell of origin, proliferation, and BCL2- or C-MYC rearrangements). We were able to reproduce data suggesting an IPI- and response to therapy independent, negative prognostic impact of CCNE in CHOP-treated DLBCL patients: CCNE-positive cases had a median survival of 16 months compared with 57 months in negative ones (p=0.012). In R-CHOP-treated patients the prognostic impact of CCNE was abrogated and only IPI, cell of origin and response to therapy had a prognostic significance. CONCLUSIONS: Addition of R to CHOP overcomes the negative prognostic impact of CCNE in DLBCL. Thus, R not only prolongs survival in DLBCL but also serves a cautionary note that prognostic factors should not be transferred into the 'R era' without proper scientific studies.
Authors: David Martín-Garcia; Alba Navarro; Rafael Valdés-Mas; Guillem Clot; Jesús Gutiérrez-Abril; Miriam Prieto; Inmaculada Ribera-Cortada; Renata Woroniecka; Grzegorz Rymkiewicz; Susanne Bens; Laurence de Leval; Andreas Rosenwald; Judith A Ferry; Eric D Hsi; Kai Fu; Jan Delabie; Dennis Weisenburger; Daphne de Jong; Fina Climent; Sheila J O'Connor; Steven H Swerdlow; David Torrents; Sergi Beltran; Blanca Espinet; Blanca González-Farré; Luis Veloza; Dolors Costa; Estella Matutes; Reiner Siebert; German Ott; Leticia Quintanilla-Martinez; Elaine S Jaffe; Carlos López-Otín; Itziar Salaverria; Xose S Puente; Elias Campo; Sílvia Beà Journal: Blood Date: 2018-12-11 Impact factor: 22.113
Authors: Jun Yin; Betsy LaPlant; Geoffrey L Uy; Guido Marcucci; William Blum; Richard A Larson; Richard M Stone; Sumithra J Mandrekar Journal: Blood Adv Date: 2019-06-11
Authors: Ondrej Havranek; Petra Kleiblova; Jan Hojny; Filip Lhota; Pavel Soucek; Marek Trneny; Zdenek Kleibl Journal: PLoS One Date: 2015-10-27 Impact factor: 3.240