RELAPSE DLBCL MOLECULAR CLASSIFICATION

	J Clin Oncol. 2011 Sep 26. [Epub ahead of print] The Germinal Center/Activated B-Cell Subclassification Has a Prognostic Impact for Response to Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Bio-CORAL Study. Thieblemont C, Briere J, Mounier N, Voelker HU, Cuccuini W, Hirchaud E, Rosenwald A, Jack A, Sundstrom C, Cogliatti S, Trougouboff P, Boudova L, Ysebaert L, Soulier J, Chevalier C, Bron D, Schmitz N, Gaulard P, Houlgatte R, Gisselbrecht C. Source Catherine Thieblemont, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Hematology; Catherine Thieblemont, Josette Briere, INSERM U728, Institut Universitaire d'hématologie, Paris VII; Catherine Thieblemont, Josette Briere, Nicolas Mounier, Philippe Gaulard, Christian Gisselbrecht, Groupe d'Etude des Lymphomes de l'Adulte; Josette Briere, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Anatomie Pathologie; Wendy Cuccuini, Jean Soulier, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Hematologie biologique, Paris; Nicolas Mounier, CHU de l'Archet- Hemato-oncology, Nice; Edouard Hirchaud, Catherine Chevalier, Remi Houlgatte, INSERM U533, Institut du thorax, Faculté de Médecine, Université de Nantes, Nantes; Loic Ysebaert, Service d'Hématologie CHU Purpan, Toulouse; Philippe Gaulard, Assistance Publique-Hôpitaux de Paris, Hopital Henri Mondor, Pathology, Créteil, France; Hans-Ullrich Voelker, Andreas Rosenwald, Institute of Pathology, University of Wuerzburg, Wuerzburg; Norbert Schmitz, ASKLEPIOS Klinik St Georg, Hamburg, Germany; Andrew Jack, University College London Hospital, London, United Kingdom; Christer Sundstrom, Uppsala University Hospital, Uppsala, Sweden; Sergio Cogliatti, St Gallen, Switzerland; Philippe Troughouboff, Emek Medical Center, Afula, Technion-Haifa, Israel; Ludmila Boudova, Medical Faculty Hospital, Charles University, Pilsen, Czech Republic; and Dominique Bron, Institut Jules Bordet, Service Hématologie, Bruxelles, Belgium. Abstract PURPOSETo evaluate the prognostic value of the cell of origin (COO) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide, carboplatin, and etoposide and followed by intensive therapy plus autologous stem-cell transplantation on the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) trial. PATIENTS AND METHODSAmong the 396 patients included on the trial, histologic material was available for a total of 249 patients at diagnosis (n = 189 patients) and/or at relapse (n = 147 patients), which included 87 matched pairs. The patient data were analyzed by immunochemistry for CD10, BCL6, MUM1, FOXP1, and BCL2 expression and by fluorescent in situ hybridization for BCL2, BCL6 and c-MYC breakpoints. The correlation with survival data was performed by using the log-rank test and the Cox model.ResultsCharacteristics of immunophenotype and chromosomal abnormalities were statistically highly concordant in the matched biopsies. In univariate analysis, the presence of c-MYC gene rearrangement was the only parameter to be significantly correlated with a worse progression-free survival (PFS; P = .02) and a worse overall survival (P = .04). When treatment interaction was tested, the germinal center B (GCB) -like DLBCL that was based on the algorithm by Hans was significantly associated with a better PFS in the R-DHAP arm. In multivariate analysis, independent prognostic relevance was found for the GCB/non-GCB the Hans phenotype interaction treatment (P = .04), prior rituximab exposure (P = .0052), secondary age-adjusted International Prognostic Index (P = .039), and FoxP1 expression (P = .047). Confirmation was obtained by gene expression profiling in a subset of 39 patients. CONCLUSIONCOO remains a major and independent factor in relapsed/refractory DLBCL, with a better response to R-DHAP in GCB-like DLBCL. This needs confirmation by a prospective study.