Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs.
%0 Journal Article
%1 Klapper.2012
%A Klapper, Wolfram
%A Kreuz, Markus
%A Kohler, Christian W.
%A Burkhardt, Birgit
%A Szczepanowski, Monika
%A Salaverria, Itziar
%A Hummel, Michael
%A Loeffler, Markus
%A Pellissery, Shoji
%A Woessmann, Wilhelm
%A Schwänen, Carsten
%A Trümper, Lorenz
%A Wessendorf, Swen
%A Spang, Rainer
%A Hasenclever, Dirk
%A Siebert, Reiner
%D 2012
%J Blood
%K Adolescent Adult Age_Factors Analysis_of_Variance Antineoplastic_Combined_Chemotherapy_Protocols/therapeutic_use Chromosome_Aberrations Comparative_Genomic_Hybridization DNA-Binding_Proteins/genetics/metabolism Gene_Expression_Profiling Gene_Expression_Regulation,_Leukemic Humans Immunohistochemistry In_Situ_Hybridization,_Fluorescence Linear_Models Lymphoma,_Large_B-Cell,_Diffuse/diagnosis/drug_therapy/genetics Middle_Aged Mutation Outcome_Assessment_(Health_Care)/methods Polycomb_Repressive_Complex_2 Prognosis Proto-Oncogene_Proteins_c-bcl-2/genetics/metabolism Transcription_Factors/genetics/metabolism Young_Adult
%N 8
%P 1882–1887
%T Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma
%V 119
%X Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs.
@article{Klapper.2012,
abstract = {Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs.},
added-at = {2014-10-13T18:24:53.000+0200},
author = {Klapper, Wolfram and Kreuz, Markus and Kohler, Christian W. and Burkhardt, Birgit and Szczepanowski, Monika and Salaverria, Itziar and Hummel, Michael and Loeffler, Markus and Pellissery, Shoji and Woessmann, Wilhelm and Schwänen, Carsten and Trümper, Lorenz and Wessendorf, Swen and Spang, Rainer and Hasenclever, Dirk and Siebert, Reiner},
biburl = {https://www.bibsonomy.org/bibtex/2b451f29888b1e02c307b6e2eadf10951/drtester},
interhash = {51894c19491a0523a4c4a76101b222f3},
intrahash = {b451f29888b1e02c307b6e2eadf10951},
journal = {Blood},
keywords = {Adolescent Adult Age_Factors Analysis_of_Variance Antineoplastic_Combined_Chemotherapy_Protocols/therapeutic_use Chromosome_Aberrations Comparative_Genomic_Hybridization DNA-Binding_Proteins/genetics/metabolism Gene_Expression_Profiling Gene_Expression_Regulation,_Leukemic Humans Immunohistochemistry In_Situ_Hybridization,_Fluorescence Linear_Models Lymphoma,_Large_B-Cell,_Diffuse/diagnosis/drug_therapy/genetics Middle_Aged Mutation Outcome_Assessment_(Health_Care)/methods Polycomb_Repressive_Complex_2 Prognosis Proto-Oncogene_Proteins_c-bcl-2/genetics/metabolism Transcription_Factors/genetics/metabolism Young_Adult},
number = 8,
pages = {1882–1887},
timestamp = {2014-10-13T18:24:53.000+0200},
title = {Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma},
volume = 119,
year = 2012
}