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The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement

From the Department of Hematology, Hôtel Dieu, University Hospital of Nantes, Place Alexis Ricordeau, 4093 Nantes cedex 01, France (SLG, CT, TG, PM, JLH); Laboratory of Hematology, Clinical Hematology Department, University Hospital, Place Alexis Ricordeau, 44093 Nantes cedex 01, France (PT, RG, H-AL); Laboratory of Anatomopathology, University Hospital, Place Alexis Ricordeau 44093 Nantes cedex 01, France (AM, FG); Centre Catherine de Sienne, 2 rue Eric Tabarly, 44200 Nantes, France (NJ-M); Department of Hematology, University Hospital, Hôpital Haut Lévèque, 3604 Pessac, France (NM)

Correspondence: Hervé Avet-Loiseau, MD, PhD, Laboratory of Hematology, Clinical Hematology Department, University Hospital, Place Alexis Ricordeau, 44093 Nantes cedex 01, France. E-mail: herve.avetloiseau{at}chu-nantes.fr

Background and Objectives: Diffuse large B-cell lymphomas (DLBCL) are common lymphomas that have been classified into three subgroups on the basis of their patterns of gene expression. The aim of this study was to characterize the clinical, biological, immunophenotypic and cytogenetic features of DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement.

Design and Methods: Sixteen cases of DLBCL with the dual translocation were identified between 1998 and January 2006. The clinical features of these cases were examined and morphological, immunohistochemical, flow cytometric and cytogenetic analyses were performed.

Results: All patients had aggressive features: B symptoms (81%), ECOG performance status >2 (81%), elevated lactate dehydrogenase (100%), stage IV disease (100%) with at least one extra-nodal localization (bone marrow, blood and central nervous system involvement in 93%, 50% and 50%, respectively) and age-adjusted IPI score of 3 in 81%. Despite intensive chemotherapy regimens (including allogeneic transplants), all patients died of disease progression. Progression-free and overall survival was 4 and 5 months, respectively. Immunophenotyping analysis (CD20, CD10, Bcl-6, Mum-1, Bcl-2 CD138, MIB1, CD19, CD5, CD38 and sIg) was performed and showed DLBCL with a germinal center (GC) profile. Ki-67 staining ranged from 70 to 90%. All cases assessed by cytogenetics analysis [conventional cytogenetic and/or fluorescence in situ hybridization (FISH)] had a complex karyotype. In one case, we identified a 8q24/c-MYC translocation variant never reported in DLBCL before: t(8;9)(q24;p13) and t(14;18)(q32;q21). The BCL-6 rearrangement was investigated by FISH and found to rearranged in four cases.

Interpretation and Conclusions: In conclusion, DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement is a subgroup of GC-DLBCLwith poor outcome. It is worth searching for the coexistence of dual translocations in Bcl-2-positive DLBCL with unusual aggressive presentation.

Key words: high grade non-Hodgkin’s lymphoma, bcl-2, c-myc.

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Comment to: The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 2007; 92:1335-1342

P Bertrand, C Maingonnat, P Ruminy, H Tilly, C Bastard
Haematologica 2008 93: e53. [Full Text] [PDF]

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				P Bertrand, C Maingonnat, P Ruminy, H Tilly, and C Bastard Comment to: The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 2007; 92:1335-1342 Haematologica, July 1, 2008; 93(7): e53 - e53. [Full Text] [PDF]

				P. Lin and L. J. Medeiros High-grade B-cell lymphoma/leukemia associated with t(14;18) and 8q24/MYC rearrangement: a neoplasm of germinal center immunophenotype with poor prognosis Haematologica, October 1, 2007; 92(10): 1297 - 1301. [Full Text] [PDF]