Bcl‐2, <scp>B</scp>cl‐6, and the <scp>I</scp>nternational <scp>P</scp>rognostic <scp>I</scp>ndex are prognostic indicators in patients with diffuse large <scp>B</scp>‐cell lymphoma treated with rituximab‐containing chemotherapy

Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Fukuhara, Suguru; Morikawa, Noriyuki; Munakata, Wataru; Maruyama, Dai; Kim, Sung-Won; Watanabe, Takashi; Kobayashi, Yasuhito; Tobinai, Kensei; Tsuda, Hitoshi

doi:10.1111/j.1349-7006.2012.02382.x

Cited by 19 publications

(24 citation statements)

References 38 publications

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“…(30,31) However, this has recently become a controversial issue. (26,32) In the present study, neither GCB versus non-GCB nor the expression of CD10, Bcl-6, or MUM1 was a significant prognostic factor for cases of DLBCL transformed from FL.…”

Section: Discussioncontrasting

confidence: 72%

“…A high Ki-67 index is reported to be a poor prognostic parameter in de novo DLBCL (25) ; however, the issue is controversial. (26) In the present study, Ki-67 was a significant predictor of PFS and OS in univariate analyses, although this significance was not sustained in multivariate analysis. We found that a 100% proportion of DLBCL in DLBCL transformed from FL displayed a worse outcome than the other groups.…”

Section: Discussioncontrasting

confidence: 69%

“…(27) Bcl-2 positivity has been reported to be associated with unfavorable prognosis in de novo DLBCL. (26,28,29) In the present study, Bcl-2 positivity predicted significantly shorter PFS in cases of DLBCL transformed from FL, and patients negative for Bcl-2 showed 100% 5-year OS. Conversely, patients with a low FL grade who were positive for IGH/BCL2 fusion tended to have poorer PFS and OS, although these results were not significant.…”

Section: Discussionsupporting

confidence: 49%

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Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

et al. 2013

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Follicular lymphoma (FL) frequently transforms into diffuse large B-cell lymphoma (DLBCL). To clarify the associated clinicopathological prognostic parameters, we examined the correlation of 11 histopathological parameters with progression-free survival (PFS) and overall survival (OS) in 107 consecutive patients who had DLBCL with pre-existing (asynchronous) or synchronous FL. The patients comprised 58 men and 49 women with a median age of 56 years. For DLBCL, the complete response rate was 81%, overall response rate was 88%, and 5-year PFS and OS rates were 55% and 79%, respectively. Immunohistochemical analysis of the DLBCL component revealed the following positivity rates: CD10, 64%; Bcl-2, 83%; Bcl-6, 88%; MUM1, 42%; GCB, 82%; cMyc index 80%, 17%; and Ki-67 index 90%, 19%. IGH/BCL2 fusion was positive in 57% of DLBCL cases. In univariate analyses, asynchronous FL and DLBCL (24%, P = 0.021), 100% proportion of DLBCL (29%, P = 0.004), Bcl-2 positivity (P = 0.04), and high Ki-67 index (P = 0.003) were significantly correlated with shorter PFS. Asynchronous FL and DLBCL (P = 0.003), 100% proportion of DLBCL (P = 0.001), and high Ki-67 index (P = 0.004) were significantly correlated with shorter OS. In a multivariate analysis, asynchronous FL and DLBCL (P = 0.035) and 100% proportion of DLBCL (P = 0.016) were significantly correlated with shorter OS. Thus, asynchronism and 100% proportion of DLBCL, that is, FL relapsed as pure DLBCL, or FL and DLBCL at different sites, were significant predictors of unfavorable outcome of patients with DLBCL transformed from FL. (Cancer Sci 2013; 104: 952-957) F ollicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma in the Western world, accounting for 22% of all cases worldwide.(1) The risk of FL transformation was reported to be approximately 20% at 8 years.(2,3) Transformation to diffuse large B-cell lymphoma (DLBCL) is observed frequently, with cells most commonly resembling centroblasts, (4) but occasionally resembling anaplastic large cells with CD30 expression.(5) In rare cases, transformation to Burkitt or Burkitt-like lymphoma (6) or precursor B-lymphoblastic lymphoma ⁄ acute lymphoid leukemia has been noted.(7) Composite FL and Hodgkin lymphoma have been suggested to represent two morphologic manifestations of the same tumor clones. (8,9) Transformation to DLBCL is frequently associated with a rapidly progressive clinical course and death from a tumor that is refractory to treatment.(3) Ghesqui eres et al. analyzed 60 DLBCLs transformed from low-grade B-cell lymphoma and reported that complete remission with multidrug chemotherapy regimens was achieved in 60% of the patients, but 48% of them relapsed. Overall survival (OS) and freedom-from-progression rates at 5 years were 57% and 33%, respectively. (10) In recent years, several analyses of genetic alterations that appear to affect the risk for FL transformation have been reported, including activation of cMYC, (6,11) inactivation of TP53, (12,13) and inactivation of p16 INK4a . (14,15) Ho...

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Section: Discussioncontrasting

confidence: 72%

Section: Discussioncontrasting

confidence: 69%

Section: Discussionsupporting

confidence: 49%

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Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

et al. 2013

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“…Bcl-6 protein is expressed in about 47–84% of DLBCLs. Bcl-6 rearrangement and Bcl-6 protein expression were reported to be associated with favorable clinical outcome [25–28]. In the present study, Bcl-2 positivity and Bcl-6 negativity were found to be parameters predicting a significantly shorter PFS particularly (Figure 2).…”

Section: Discussionsupporting

confidence: 61%

Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: A phase II study

Cao

et al. 2016

Oncotarget

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Cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab (R-CHOP) is the standard treatment for patients with diffuse large B cell lymphoma (DLBCL). However, rituximab cannot be popularly applied in a considerable number of patients with DLBCL because of economic reasons. To develop a new regimen to improve the outcome of these patients is extremely important. In our study, sixty five patients with DLBCL were randomly assigned to thalidomide plus CHOP group (n=32) or to CHOP alone group (n=33). Objective response rates (ORR) and complete remission rates (CRR) were 96.7% and 80.6% in T-CHOP group versus 78.9 % and 57.8 % in CHOP group, respectively (P <0.05). At a median follow-up of 96 months, median PFS for T-CHOP group was still not reached yet, and in CHOP group it was 22.9 months (95% CI [0-50.4]). (P=0.163). Median overall survival (OS) for T-CHOP group was also not reached, and the estimated median OS for CHOP group was 83.5 months, the difference of OS between the two groups is not significant (p=0.263). But, in patients with Bcl-2 positive and Bcl-6 negative, the median PFS in T-CHOP group was longer than that in CHOP group (111.0 vs 8.5 months (P=0.017). In addition, thalidomide did not significantly increase the grade 3/4 toxicity of CHOP. We concluded that the addition of thalidomide to the CHOP regimen significantly improved the CRR and showed a trend of improving clinical outcome in patients with DLBCL, especially for patients with Bcl-2 positive and Bcl-6 negative B-cell phenotype, without increased toxicity.

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“…Protein expression has been associated with poor outcome in most studies (21,30–32). However, its survival impact appears to be modulated by rituximab (33,34).…”

Section: Resultsmentioning

confidence: 99%

Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies

Coutinho

Clear

Owen

et al. 2013

Clinical Cancer Research

107

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Purpose The opportunity to improve therapeutic choices on the basis of molecular features of the tumour cells is on the horizon in Diffuse Large B-cell Lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. While molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However results are poorly reproducible by independent groups. Experimental design We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1 and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan-Meier curves and the log-rank test. Results The concordance in patient’s classification across the different algorithms was low. Only 4% the tumors have been classified as GCB and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP treated cohort. Conclusion Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions.

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Bcl‐2, Bcl‐6, and the International Prognostic Index are prognostic indicators in patients with diffuse large B‐cell lymphoma treated with rituximab‐containing chemotherapy

Cited by 19 publications

References 38 publications

Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: A phase II study

Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies

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