Clinicopathologic Characteristics and Outcome of Diffuse Large B-Cell Lymphomas Presenting With an Associated Low-Grade Component at Diagnosis

2006 ◽  
Vol 24 (33) ◽  
pp. 5234-5241 ◽  
Author(s):  
Hervé Ghesquières ◽  
Françoise Berger ◽  
Pascale Felman ◽  
Evelyne Callet-Bauchu ◽  
Paul-André Bryon ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Complete Response ◽  
Progression Rate ◽  
Low Grade ◽  
Control Analysis ◽  
B Cell Lymphomas ◽  
Response To Chemotherapy ◽  
Large B Cell

Purpose Some diffuse large B-cell lymphomas (DLBCL) present at diagnosis with associated morphologic features of small B-cell non-Hodgkin's lymphoma (NHL) and may arise from the transformation of a previously unknown indolent low-grade lymphoma. The characteristics and prognosis of these particular DLBCL are not well known. Patients and Methods The strict morphologic review of consecutive DLBCL patients diagnosed over 12 years in our department (Hematology Department, Centre Hospitalier Lyon-Sud, Lyon, France) allowed to retrieve 60 DLBCL that could be have occurred from the transformation of marginal zone B-cell NHL (32 patients), follicular NHL (22 patients), and small lymphocytic NHL (6 patients). We compared them to 180 matched patients of de novo DLBCL. Results Patients median age was 55 years and presented the following clinical characteristics: poor performance status in 33%, disseminated disease in 97%, more than one extranodal site in 50%, and increased lactate dehydrogenase level in 55%. Complete remission with multidrug chemotherapy regimens was achieved in 60% of the patients, but 48% relapsed: 28% with aggressive and 20% with indolent histology, respectively. Overall survival (OS) and freedom-from-progression rates at 5 years were 57% and 33%, respectively. The matched-control analysis showed that patients with transformed NHL at diagnosis had lower complete response to chemotherapy (P = .004) and higher progression rate (P = .03), whereas no difference was observed in OS (P = .21). Conclusion Compared to de novo DLBCL, transformed NHL at diagnosis have similar overall survival but lower complete response to initial treatment and higher risk of indolent relapses.

T-Cell/Histiocyte-Rich Large B-Cell Lymphomas and Classical Diffuse Large B-Cell Lymphomas Have Similar Outcome After Chemotherapy: A Matched-Control Analysis

2003 ◽  
Vol 21 (7) ◽  
pp. 1271-1277 ◽  
Author(s):  
R. Bouabdallah ◽  
N. Mounier ◽  
C. Guettier ◽  
T. Molina ◽  
V. Ribrag ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Matched Control ◽  
Disease Risk ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Control Analysis ◽  
B Cell Lymphomas ◽  
Response To Chemotherapy ◽  
Large B Cell

Purpose: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). Patients and Methods: More than 4,500 patients were enrolled onto non-Hodgkin’s lymphoma trials conducted by the Groupe d’Etude des Lymphomes de l’Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). Results: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was ≥ 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean ± SD) were 58% ± 18% and 53% ± 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P = .06), whereas no difference was observed in OS (P = .9) and EFS (P = .8). Conclusion: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.

T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.

1995 ◽  
Vol 13 (7) ◽  
pp. 1742-1750 ◽  
Author(s):  
J P Greer ◽  
W R Macon ◽  
R E Lamar ◽  
S N Wolff ◽  
R S Stein ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Combination Chemotherapy ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
B Cell Lymphomas ◽  
Intermediate Grade ◽  
Large B Cell

PURPOSE Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.

Novel Fusion of the MALT1/MLT and MAP4 Genes Detected in a Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2838-2838
Author(s):  
Eva M. Murga Penas ◽  
Kristina Hinz ◽  
Petra Behrmann ◽  
Martin L. Hansmann ◽  
Claudia Becher ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Rt Pcr ◽  
B Cell Lymphomas ◽  
Specific Primers ◽  
Interphase Fish ◽  
Exon 9 ◽  
Race Pcr ◽  
Large B Cell

Abstract The MALT1/MLT gene codes for a human paracaspase and plays a crucial role in NF-κB activation in response to TCR induction. Rearrangements of MALT1/MLT by the translocations t(11;18)(q21;q21) and t(14;18)(q32;q21) act by activating the NF-κB pathway and are the most frequent structural chromosomal abnormalities in extranodal marginal zone B-cell lymphomas of the MALT-type. They occur in 20 to 50% of low grade MALT lymphomas, but with only rare exception are absent in diffuse large B-cell lymphomas (DLBCL). By screening 118 diffuse large B-cell lymphomas and 28 Burkitt’s lymphomas by interphase FISH with probes flanking MALT1/MLT (Abbott Vysis), we found two cases with a break within MALT1/MLT. Further experiments with plasmid subclones from the BAMH1 fragments of PAC 152M5, which spans the entire coding region of MALT1/MLT, confirmed the break within MALT1/MLT in one case. This patient presented with a relapse of a DLBCL, centroblastic subtype, without any concomitant low-grade component or lymphoepithelial lesions. During relapse only nodal manifestations were seen (stage IIIA), however, at the time of primary diagnosis a lymphoma infiltration of one adrenal gland was present. FISH experiments with MALT1/MLT, API2 and IGH specific probes did not identify a t(11;18) or a t(14;18). 3′ RACE-PCR revealed a novel in frame fusion of exon 9 of the MALT1/MLT gene and exon 9 of the microtubule-associated protein 4 (MAP4) gene. RT-PCR with specific primers for MALT1/MLT and MAP4 confirmed the presence of the fusion transcript MALT1/MLT-MAP4. In addition, interphase FISH showed that the translocation was accompanied by a deletion of MALT1/MLT sequences distal to the breakpoint including the caspase-like domain, which is essential for activation of the NF-κB pathway in MALT lymphomas. Corresponding to this result, 5′ RACE-PCR with specific primers for MALT1/MLT and RT-PCR with nested primers for MAP4 and MALT1/MLT did not detect the reciprocal 5′MAP4-3′MALT1/MLT transcript. The MAP4 gene on chromosome 3p21 is the major microtubule-associated protein in non-neuronal tissues and promotes microtubule polymerization. Disruption of the microtubule-dynamics is induced by microtubule-interfering drugs, such as taxanes and Vinca alkaloids. We conclude that the 5′MALT1/MLT-3′MAP4 fusion is the pathogenetically relevant transcript in this non-reciprocal der(18)t(3;18)(p21;q21) translocation. The absence of the caspase like domain distinguishes this novel gene fusion, MALT1/MLT-MAP4, from the API2-MALT1/MLT in the t(11;18) and the IGH-MALT1/MLT in the t(14;18), in which the caspase like domain is invariably present and points to MAP4 as a new target gene with possible therapeutic implications in DLBCL.

Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8040-8040 ◽  
Author(s):  
K. Fu ◽  
K. D. Perry ◽  
L. M. Smith ◽  
C. P. Hans ◽  
T. C. Greiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8040 Background: Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subgroups, i.e. germinal center B-cell (GCB) and activated B-cell (ABC) DLBCL, which were initially characterized by gene expression profiling and subsequently validated by immunostaining. Bcl-2 has also been identified as a prognostic indicator in the ABC subgroup. However, with the addition of rituximab (R) to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Methods: We studied 119 cases of de novo DLBCL including 70 cases treated with R-CHOP and 49 cases treated with CHOP. The cases were assigned to either the GCB or non-GCB subgroups using the methodology described by Hans et al (Blood 2004; 103:275). Characteristics of the patients were compared using the Chi-square test. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan Meier method and compared with the log-rank test. Results: The median age of the 119 patients was 67 years, ranging from 20 to 90 years, and there were 62 males and 57 females. The clinical characteristics of patients treated with CHOP versus R-CHOP, including the IPI, were comparable. R-CHOP was more effective than CHOP with improved 5-year EFS (63% vs 41%, p=0.013) and OS (78% vs 47%, p<0.001). In both patient groups treated with R-CHOP or CHOP, the GCB subgroup had a significantly better 5-year EFS and OS compared to the non-GCB subgroup (OS: 91% vs 64% for R-CHOP, p=0.0073; 67% vs 31% for CHOP, p=0.034, respectively). Additionally, both the GCB and non-GCB subgroups treated with R-CHOP had a significantly improved OS compared to their respective subgroups receiving CHOP alone (GCB, p=0.015; non-GCB, p=0.019). Bcl-2 expression was not a significant predictor in either the GCB or non-GCB subgroups treated with R-CHOP (OS, GCB: p=0.32; non-GCB: p=0.43). Conclusions: In this retrospective study, we demonstrate that subclassification based on the cell of origin continues to have prognostic significance in patients with DLBCL treated with R-CHOP. Addition of rituximab to CHOP improves the overall survival of patients with DLBCL in both the GCB and non-GCB subgroups. No significant financial relationships to disclose.

scholarly journals CD5 expression in de novo diffuse large B-cell lymphomas

2009 ◽  
Vol 20 (4) ◽  
pp. 789-790 ◽  
Author(s):  
P. Went ◽  
A. Zimpfer ◽  
A. Tzankov ◽  
S. Dirnhofer
Keyword(s):  
B Cell ◽  
De Novo ◽  
B Cell Lymphomas ◽  
Large B Cell

scholarly journals A Short Mutational Hot Spot in the First Intron of BCL-6 Is Associated with Increased BCL-6 Expression and with Longer Overall Survival in Large B-Cell Lymphomas

2002 ◽  
Vol 160 (4) ◽  
pp. 1371-1380 ◽  
Author(s):  
María-Jesús Artiga ◽  
Ana-Isabel Sáez ◽  
Cristina Romero ◽  
Margarita Sánchez-Beato ◽  
Mari-Sol Mateo ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Hot Spot ◽  
B Cell Lymphomas ◽  
First Intron ◽  
Large B Cell

Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 699-702 ◽  
Author(s):  
Tiemo Katzenberger ◽  
Andreas Lohr ◽  
Stephan Schwarz ◽  
Martin Dreyling ◽  
Julia Schoof ◽  
...  
Keyword(s):  
B Cell ◽  
Progenitor Cell ◽  
Somatic Mutations ◽  
De Novo ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Cytogenetic Analyses ◽  
Trisomy 3 ◽  
Large B Cell

CD5+ diffuse large B-cell lymphomas (DLBLs) have recently been described as a particular subgroup of DLBLs. Classical banding and interphase cytogenetic analyses targeting ATM, TP53, and P16INK4a genes and theD13S25 locus from 13 CD5+ DLBLs were compared with 55 CD5− DLBLs. Additionally, analysis of somatic mutations of the immunoglobulin heavy chain variable region (IgVH) genes were performed in CD5+ DLBLs. CD5+DLBLs were somatically mutated (7 of 8 cases) and were negative for t(11;14)(q13;q32) and t(14;18)(q32;q21), whereas t(3;14)(q27;q32) was found in only one tumor. Trisomy 3 and gains on chromosomes 16/16p and 18/18q were significantly overrepresented in CD5+DLBLs. No ATM deletions were detected. The prevalence of deletions at the D13S25 locus was significantly higher in CD5+ DLBLs (4 of 12 [33%]) compared with CD5− DLBLs (4 of 42 [10%]), as were p16INK4a deletions (33% versus 8%). On the basis of these findings, CD5+ DLBLs are likely to arise from the same progenitor cell as the mutated variant of CD5+ lymphocytic lymphoma/B-cell chronic lymphocytic leukemia (B-CLL).

scholarly journals The Role of Consolidative Radiotherapy after a Complete Response to Chemotherapy in the Treatment of Diffuse Large B-Cell Lymphoma in the Rituximab Era: Results from a Systematic Review with a Meta-Analysis

2015 ◽  
Vol 134 (2) ◽  
pp. 111-118 ◽  
Author(s):  
Chunhong Hu ◽  
Chao Deng ◽  
Wen Zou ◽  
Guangsen Zhang ◽  
Jingjing Wang
Keyword(s):  
Systematic Review ◽  
B Cell ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Response To Chemotherapy ◽  
Large B Cell

Background: The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). The role of radiotherapy (RT) after complete response (CR) to RCHOP in patients with DLBCL remains unclear. This systematic review with a meta-analysis is an attempt to evaluate this role. Methods: Studies that evaluated RT versus no-RT after CR to RCHOP for DLBCL patients were searched in databases. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were calculated using a random-effects model. Results: A total of 4 qualified retrospective studies (633 patients) were included in this review. The results suggested that RT improved overall survival (OS; HR 0.33, 95% CI 0.14-0.77) and progression-free/event-free survival (PFS/EFS; HR 0.24, 95% CI 0.11-0.50) in all patients compared with no-RT. In a subgroup analysis of patients with stage III-IV DLBCL, RT improved PFS/EFS (HR 0.19, 95% CI 0.07-0.51) and local control (HR 0.12, 95% CI 0.03-0.44), with a trend of improving OS (HR 0.35, 95% CI 0.12-1.05). Conclusion: Consolidation RT could significantly improve outcomes of DLBCL patients who achieved a CR to RCHOP. However, the significance of these results was limited by these retrospective data. Further investigation of the role of consolidation RT in the rituximab era is needed.

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