TORNA ALL’ELENCO

ABC subtype, TP53 mutation and BCL2 overexpression are associated with a worse outcome in untreated poor-risk young diffuse large B-cell lymphoma: Results from the frontline phase iii bio-DLBCL04 study of the fondazione italiana linfomi in Blood

2017
AO Alessandria

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (25)Vedi tutti...

Chiappella A
On Behalf of Fondazione Italiana Linfomi, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
Agostinelli C
University of Bologna, Bologna, Italy
Ladetto M
Division of Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

et alii...

Abstract

Introduction. Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by cell of origin (COO) subgroups at different prognosis; in addition, the overexpression of MYC and BCL2 or the chromosomal rearrangements of MYC and BCL2 are associated with a worse outcome. The role of TP53 mutation is clear in chronic lymphocytic leukemia, but it is not yet established in DLBCL. The phase III randomized study FIL-DLCL04 in 399 young patients with untreated DLBCL at poor prognosis (age adjusted IPI, aa-IPI, 2-3), showed an advantage in term of failure-free survival (FFS) of an abbreviated Rituximab-dose-dense chemotherapy at two different dose-escalation (R-CHOP14 or R-MegaCHOP14) followed by an intensification with Rituximab-MAD+BEAM and ASCT (R-HDC+ASCT) compared to a full course of R-dose-dense chemotherapy alone (R-dose-dense). However, there was no difference in overall survival (OS). (Chiappella et al, Lancet Oncol 2017). Aims. The aim of BIO-DLCL04 was to correlate the COO profile and the presence of biomarkers (MYC and BCL2 expression, MYC and BCL2 translocations and TP53 mutation), with OS. Methods. COO subtyping was determined with immunohistochemistry (IHC) (germinal center (GCB) and non-GCB according to Hans' algorithm) and with gene expression profiling (GEP) using the NanoString Research Use Only Lymphoma Subtyping (NanoString Technologies, Inc., Seattle, WA, USA) identifying GCB, activated B-cell (ABC) and unclassified subgroups. Expression of BCL2, MYC and TP53 were studied in IHC; cases were deemed positive if at least 50%, 40% of lymphoma cells were stained with BCL2, MYC antibodies, respectively. BCL2 and MYC translocations, copy gains and aberrations were tested with fluorescent in situ hybridization (FISH) and TP53 anomalies by Sanger sequencing. Results. From 2005 to 2010, 399 DLBCL were enrolled in FIL-DLCL04 and randomized to receive R-HDC+ASCT in 199 and R-dose-dense in 200 (NCT00499018). Central histology revision was mand

Keywords

biological marker; biological product; cyclophosphamide plus doxorubicin plus prednisolone plus rituximab plus vincristine; endogenous compound; protein bcl 2; protein p53; rituximab; unclassified drug; adult; cancer chemotherapy; cancer prognosis; cancer survival; clinical outcome; conference abstract; controlled study; diffuse large B cell lymphoma; dose densification; drug therapy; failure free survival; female; fluorescence in situ hybridization; follow up; gender; gene expression profiling; gene overexpression; genetic association; genetic marker; genetic susceptibility; germinal center; hazard ratio; human; human cell; human tissue; immunohistochemistry; major clinical study; male; oncogene myc; overall survival; phase 3 clinical trial; prognosis; prospective study; randomized controlled trial; Sanger sequencing; transplantation; wild type;