Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy.

Germinal center (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL) and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. To determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome, GC and non-GC phenotypes were identified immunohistochemically from samples of 90 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). One hundred and four patients previously treated with chemotherapy served as a control group. Consistent with previous studies, chemotherapy-treated patients with immunohistochemically defined GC phenotype displayed a significantly better overall (OS) and failure-free survival (FFS) than the non-GC group (OS, 70% vs 47%, P = .012; FFS, 59% vs 30%, P = .001). In contrast, immunohistochemically defined GC phenotype did not predict outcome in immunochemotherapy-treated patients (OS, 77% vs 76%, P = ns; FFS, 68% vs 63%, P = ns). In comparison, International Prognostic Index (IPI) could separate the high-risk patients from low- and intermediate-risk groups (OS, 84% vs 63%, P = .030; FFS, 79% vs 52%, P = .028). We conclude that rituximab in combination with chemotherapy seems to eliminate the prognostic value of immunohistochemically defined GC- and non-GC phenotypes in DLBCL.

[1]  R. Gascoyne,et al.  Clinical Trials and Observations , 2005 .

[2]  Wen-yu Li,et al.  CHOP-Like Chemotherapy Plus Rituximab Versus CHOP-Like Chemotherapy Alone in Young Patients with Good-Prognosis Diffuse Large-B-Cell Lymphoma:A Randomised Controlled Trial by the MabThera International Trial (MInT) Group , 2007 .

[3]  K. Ribeiro,et al.  BCL2 Expression Is a Prognostic Marker for the Activated B-Cell-Like Type of Diffuse Large B-Cell Lymphoma. , 2006 .

[4]  L. Staudt,et al.  DA-EPOCH-R Is Highly Effective in Both BCL-6+ and BCL-6− Untreated De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Study Update and Analysis of Survival Outcomes for Multiple Biomarkers. , 2006 .

[5]  C. Blomqvist,et al.  Does Rituximab Influence the Prognostic Effect of Germinal Centre Phenotype in Diffuse Large B-Cell Lymphoma?. , 2006 .

[6]  R. Gascoyne,et al.  Addition of Rituximab (R) to CHOP Improves Survival in the Non-GCB Subtype of Diffuse Large B Cell Lymphoma (DLBCL). , 2006 .

[7]  S. Tomoyasu,et al.  Treatment Effect of Rituximab Plus Chemotherapy Is Obtained by Improving Survival from Non-Germinal Center-Type Untreated Diffuse Large B-Cell Lymphoma. , 2006 .

[8]  E. Schuuring,et al.  Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  P. De Baetselier,et al.  Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions. , 2006, Blood.

[10]  P. Westermark,et al.  Misclassification of amyloidosis is unwarranted. , 2006, Blood.

[11]  Randy D Gascoyne,et al.  Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  W. Grody,et al.  [Diffuse large B-cell lymphoma]. , 2006 .

[13]  R. Gascoyne,et al.  Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. , 2006, Blood.

[14]  J. Armitage,et al.  Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma. , 2006, Clinical lymphoma & myeloma.

[15]  A. López-Guillermo,et al.  CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. , 2006, The Lancet. Oncology.

[16]  A. Olshen,et al.  Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL. , 2005, Blood.

[17]  P. de Paepe,et al.  Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  R. Gascoyne,et al.  Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  R. Rosenquist,et al.  Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis , 2005, Modern Pathology.

[20]  B. Bonavida,et al.  Cellular and molecular signal transduction pathways modulated by rituximab (rituxan, anti-CD20 mAb) in non-Hodgkin's lymphoma: implications in chemosensitization and therapeutic intervention , 2005, Oncogene.

[21]  G. Cheng,et al.  Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. , 2005, Cancer research.

[22]  B. Bonavida,et al.  Respectively Resistance and Chemoresistance , in FasLActivity : Role of YY 1 and Bcl-x B κ Lymphoma Cell Line via Inhibition of NF-Expression in Ramos Non-Hodgkin ' sLBcl-x Rituximab-Induced Inhibition of YY 1 and Benjamin Bonavida , 2005 .

[23]  L. Staudt,et al.  Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. , 2004, Blood.

[24]  P. Gaulard,et al.  Rituximab plus CHOP (R-CHOP) overcomes bcl-2--associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). , 2003, Blood.

[25]  Emili Montserrat,et al.  Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. , 2003, Blood.

[26]  B. E. C. Oiffier,et al.  CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma , 2002 .

[27]  Meland,et al.  The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. , 2002, The New England journal of medicine.

[28]  Ulrich Siebenlist,et al.  Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells , 2001, The Journal of experimental medicine.

[29]  R Tibshirani,et al.  Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma. , 2001, Blood.

[30]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[31]  J Hermans,et al.  Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. , 1998, Blood.

[32]  J C Reed,et al.  Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. , 1997, Blood.

[33]  P. Gaulard,et al.  Prognostic Significance of bcl-2 Protein Expression in Aggressive Non-Hodgkin's Lymphoma , 1996 .

[34]  J Diebold,et al.  Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA). , 1996, Blood.

[35]  Emili Montserrat,et al.  A predictive model for aggressive non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.