High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy

Teresa M. Cardesa-Salzmann, Luis Colomo, Gonzalo Gutierrez, Wing C. Chan, Dennis Weisenburger, Fina Climent, Eva González-Barca, Santiago Mercadal, Leonor Arenillas, Sergio Serrano, Ray Tubbs, Jan Delabie, Randy D. Gascoyne, Joseph M. Connors, Jose L. Mate, Lisa Rimsza, Rita Braziel, Andreas Rosenwald, Georg Lenz, George WrightElaine S. Jaffe, Louis Staudt, Pedro Jares, Armando López-Guillermo, Elias Campo

Research output: Contribution to journalArticle

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Abstract

Background: Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods: One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results: Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P=0.004) and in the validation cohort (57% vs. 81%; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)]. Conclusions: These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.

Original languageEnglish (US)
Pages (from-to)996-1001
Number of pages6
JournalHaematologica
Volume96
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
Microvessels
Drug Therapy
Lymphoma
Survival
Leukemia
Rituximab
Tumor Microenvironment
Gene Expression Profiling
Multivariate Analysis
Clinical Trials

Keywords

  • Aggressive non-Hodgkin's lymphoma
  • Central nervous system
  • Kidney
  • Rituximab

ASJC Scopus subject areas

  • Hematology

Cite this

Cardesa-Salzmann, T. M., Colomo, L., Gutierrez, G., Chan, W. C., Weisenburger, D., Climent, F., ... Campo, E. (2011). High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. Haematologica, 96(7), 996-1001. https://doi.org/10.3324/haematol.2010.037408

High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. / Cardesa-Salzmann, Teresa M.; Colomo, Luis; Gutierrez, Gonzalo; Chan, Wing C.; Weisenburger, Dennis; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Arenillas, Leonor; Serrano, Sergio; Tubbs, Ray; Delabie, Jan; Gascoyne, Randy D.; Connors, Joseph M.; Mate, Jose L.; Rimsza, Lisa; Braziel, Rita; Rosenwald, Andreas; Lenz, Georg; Wright, George; Jaffe, Elaine S.; Staudt, Louis; Jares, Pedro; López-Guillermo, Armando; Campo, Elias.

In: Haematologica, Vol. 96, No. 7, 07.2011, p. 996-1001.

Research output: Contribution to journalArticle

Cardesa-Salzmann, TM, Colomo, L, Gutierrez, G, Chan, WC, Weisenburger, D, Climent, F, González-Barca, E, Mercadal, S, Arenillas, L, Serrano, S, Tubbs, R, Delabie, J, Gascoyne, RD, Connors, JM, Mate, JL, Rimsza, L, Braziel, R, Rosenwald, A, Lenz, G, Wright, G, Jaffe, ES, Staudt, L, Jares, P, López-Guillermo, A & Campo, E 2011, 'High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy', Haematologica, vol. 96, no. 7, pp. 996-1001. https://doi.org/10.3324/haematol.2010.037408
Cardesa-Salzmann, Teresa M. ; Colomo, Luis ; Gutierrez, Gonzalo ; Chan, Wing C. ; Weisenburger, Dennis ; Climent, Fina ; González-Barca, Eva ; Mercadal, Santiago ; Arenillas, Leonor ; Serrano, Sergio ; Tubbs, Ray ; Delabie, Jan ; Gascoyne, Randy D. ; Connors, Joseph M. ; Mate, Jose L. ; Rimsza, Lisa ; Braziel, Rita ; Rosenwald, Andreas ; Lenz, Georg ; Wright, George ; Jaffe, Elaine S. ; Staudt, Louis ; Jares, Pedro ; López-Guillermo, Armando ; Campo, Elias. / High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. In: Haematologica. 2011 ; Vol. 96, No. 7. pp. 996-1001.
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abstract = "Background: Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods: One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results: Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54{\%} vs. 78{\%}; P=0.004) and in the validation cohort (57{\%} vs. 81{\%}; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)]. Conclusions: These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.",
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author = "Cardesa-Salzmann, {Teresa M.} and Luis Colomo and Gonzalo Gutierrez and Chan, {Wing C.} and Dennis Weisenburger and Fina Climent and Eva Gonz{\'a}lez-Barca and Santiago Mercadal and Leonor Arenillas and Sergio Serrano and Ray Tubbs and Jan Delabie and Gascoyne, {Randy D.} and Connors, {Joseph M.} and Mate, {Jose L.} and Lisa Rimsza and Rita Braziel and Andreas Rosenwald and Georg Lenz and George Wright and Jaffe, {Elaine S.} and Louis Staudt and Pedro Jares and Armando L{\'o}pez-Guillermo and Elias Campo",
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T1 - High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy

AU - Cardesa-Salzmann, Teresa M.

AU - Colomo, Luis

AU - Gutierrez, Gonzalo

AU - Chan, Wing C.

AU - Weisenburger, Dennis

AU - Climent, Fina

AU - González-Barca, Eva

AU - Mercadal, Santiago

AU - Arenillas, Leonor

AU - Serrano, Sergio

AU - Tubbs, Ray

AU - Delabie, Jan

AU - Gascoyne, Randy D.

AU - Connors, Joseph M.

AU - Mate, Jose L.

AU - Rimsza, Lisa

AU - Braziel, Rita

AU - Rosenwald, Andreas

AU - Lenz, Georg

AU - Wright, George

AU - Jaffe, Elaine S.

AU - Staudt, Louis

AU - Jares, Pedro

AU - López-Guillermo, Armando

AU - Campo, Elias

PY - 2011/7

Y1 - 2011/7

N2 - Background: Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods: One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results: Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P=0.004) and in the validation cohort (57% vs. 81%; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)]. Conclusions: These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.

AB - Background: Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods: One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results: Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P=0.004) and in the validation cohort (57% vs. 81%; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)]. Conclusions: These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.

KW - Aggressive non-Hodgkin's lymphoma

KW - Central nervous system

KW - Kidney

KW - Rituximab

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