[1456] Clinical Impact of MYC, BCL2, BCL6, and MALT1 Alterations in Diffuse Large B-Cell Lymphoma (DLBCL) in the Rituximab (R) Era

S Valera, T Cardesa, F Climent, V Romagosa, E Gonzalez, L Arenillas, S Serrano, JL Mate, O Salamero, A Lopez-Guillermo, E Campo, L Colomo. H. Clinic, Barcelona, Spain; H. de Bellvitge, Barcelona, Spain; H. del Mar, Barcelona, Spain; H. Germans Tries, Badalona, Grup Estudi Limfomes Catalunya i Balears (GELCAB), Spain

Background: The addition of R to the classic schemes of DLBCL has significantly improved the course of the disease. The impact of the genetic alterations has to be revisited.
Design: We have investigated the prognostic impact of the genetic alterations involving MYC, BCL2, BCL6 and MALT1 genes in a series of 126 patients with de novo DLBCL diagnosed between 2002 and 2007. FISH break-apart probes (Dako) were used, and translocations and gains were assessed in order to study their significance. Mediastinal, plasmablastic and immunosuppresion-associated lymphomas were excluded. Moreover, clinical, morphological and immunophenotypic profiles determined by the Hans classifier were correlated. 111 (88%) patients were treated with schemes including R (95 R-CHOP; 8 R-COP; 8 R-CHOP-ESHAP). 7(6%) did not receive treatment, 5(4%) received monotherapy, and 3(2%) only CHOP.
Results: The table summarizes the frequencies of the genetic alterations.

MYCBCL2BCL6MALT1
Translocations13 (10%)19 (15%)32 (26%)0
Gains19 (15%)28 (22%)31 (26%)33 (28%)
No alterations94 (75%)78 (63%)60 (48%)86 (72%)
Total (N)126125123119


MYC-only alterations occurred in 3 patients (2.5%); double hits involving MYC-BCL2, and MYC-BCL6 occurred in 5(4%) and 3(2.5%) patients, respectively; 2(1.7%) cases had a triple hit MYC-BCL2-BCL6. MYC and BCL2 translocations significantly associated with high IPI scores, whereas only BCL2 and MALT1 alterations presented at high stages (all p<0.05). No other associations with clinical parameters were significant in this series. Phenotypically, MYC and BCL2 translocations presented in the GC-DLBCL (p=0.019 and p=0.001, respectively), whereas BCL6 amplifications associated with the ABC-DLBCL (p=0.001). BCL2 and MALT1 were significantly coamplified (p<0.005). MYC translocations, but neither MYC gains nor BCL2, BCL6 and MALT1 alterations had impact on the overall survival (OS)(median survival 1.3 years; range 0.6-2.2; p=0.005). Double and triple hit translocations also decreased significantly the OS (median survival 1.4 years; range 0-2; p=0.023).
Conclusions: MYC translocations may be associated with additional translocations of BCL2 and BCL6, and have a relevant impact in the OS of patients with DLBCL.
Category: Hematopathology

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 174, Wednesday Morning

 

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