Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL (original) (raw)
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Blood, 2016
Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called 'double hit' lymphoma has been associated with a high risk of central nervous system (CNS) relapse; however the impact of dual expression of both MYC and BCL2 ('dual expressers') on the risk of CNS relapse remains unknown. Pre-treatment formalin fixed paraffin embedded DLBCL biopsies derived from patients subsequently treated with R-CHOP were…
Leukemia & lymphoma, 2017
Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1.3, 4.6, 8.8, and 12.7% in the low-, low-intermediate-, high-intermediate-, and high-risk groups, respectively (p <.001). This result is comparable with that of the CNS-IPI. Patients with breast involvement tended to have lower risk according to the standard IPI but showed frequent CNS involvement, similar to patients with testis involvement. The standard IPI is also a useful predictor of CNS involvement. Patients with breast/testis involvement would be candidates for prophylaxi...
Haematologica, 2017
The objective of this study was to create a bio-clinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group LY12 prospective study. Sufficient histologic material was available for 91 cases to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and pySTAT3 expression. 67 cases had material sufficient for fluorescent in-situ hybridization for MYC and BCL2. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent digital gene expression profiling to evaluate BCL2, MYC, P53, and STAT3 expression, and to determine Cell-of-Origin using the Lymph2Cx assay. No method of determining Cell-of Origin predicted event-free or overall survival. Factors independently associated with survival outcomes in multivariate analysis included primary refractory disease, elevated s...
Clinical Lymphoma Myeloma and Leukemia, 2021
The prognostic significance of B-cell lymphoma 2 (BCL2) expression in patients with diffuse large B-cell lymphoma (DLBCL) is conflicting. We developed an immunohistochemistry (IHC) algorithm and assay to determine BCL2 expression and assessed the prognostic value of BCL2 in newly diagnosed DLBCL cohorts. BCL2 expression was associated with poorer progression-free survival. Findings support use of our BCL2 IHC scoring system and assay to select BCL2-positive patients for future studies. Introduction: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts. Patients and Methods: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells. Functionally relevant cutoffs were based on the sensitivity of lymphoma cell lines to venetoclax. This assay was highly reproducible across laboratories. The prognostic impact of BCL2 expression was assessed in DLBCL patients from the phase 3 MAIN (n ¼ 230) and GOYA (n ¼ 366) trials, and a population-based registry (n ¼ 310). Results: Approximately 50% of tumors were BCL2 positive, with a higher frequency in high International Prognostic Index (IPI) and activated Bcellelike DLBCL subgroups. BCL2 expression was associated with poorer progression-free survival in the MAIN study (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.81-3.40; multivariate Cox regression adjusted for IPI and cell of origin). This trend was confirmed in the GOYA and registry cohorts in adjusted multivariate analyses (GOYA: HR, 1.72; 95% CI, 1.05-2.82; registry: HR, 1.89; 95% CI, 1.29-2.78). Patients with BCL2 immunohistochemistry-positive and IPIhigh disease had the poorest prognosis: 3-year progression-free survival rates were 51% (GOYA) and 37% (registry). Conclusion: Findings support use of our BCL2 immunohistochemistry scoring system and assay to select patients with BCL2-positive tumors for future studies.
Blood Cancer Journal, 2021
We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007–2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7–66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7–24.6,n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5–3.6,n = 118) overall, and 8.0% (95% CI: 6.0–10.6,n = 48) among patients with high CNS-IPI (4–6), when considering other relapse locations and death as compet...
Bcl-6 predicts improved prognosis in primary central nervous system lymphoma
Cancer, 2007
BACKGROUND. In systemic non-Hodgkin lymphoma (NHL), tumors that resemble germinal center B-cells are less aggressive than tumors that resemble postgerminal center B-cells. However, the value of B-cell differentiation markers in primary central nervous system lymphoma (PCNSL) is less clear. The objectives of this study were to characterize the immunophenotypes of PCNSL samples and to determine their utility in predicting clinical outcomes. METHODS. The immunohistochemical staining profile of PCNSL was determined from 66 immunocompetent patients. Then, the authors evaluated whether the expression of these proteins was associated with progression-free or overall survival. RESULTS. Only 8% of PCNSL samples were positive for the cluster designation (CD) germinal center marker CD10. Another germinal center marker, bcl-6, was positive in 47% of samples. Ninety-four percent of samples expressed significant levels of the postgerminal center marker melanoma-associated antigen (MUM-1). In univariate analyses, only bcl-6 staining had a significant effect on progressionfree survival (median, 20.5 months in bcl-6-positive patients vs 10.1 months in bcl-6-negative patients; P 5 .02). There was a nonsignificant trend toward improved overall survival in patients who had bcl-6 expressing tumors. Older age and poorer performance status, as observed previously, were associated with reduced survival. CONCLUSIONS. Bcl-6 expression was associated with a better prognosis in
Archives of the Balkan Medical Union
L'impact de l'expression combinée de MYC, BCL2 et BCL6 sur la survie des patients atteints de lymphome diffus à grandes cellules B Introduction. C-MYC est l'un des facteurs de transcription essentiels qui jouent un rôle dans diverses fonctions cellulaires. Le réarrangement MYC est associé à une faible survie globale et une faible survie sans progression, un risque accru de rechute du système nerveux central chez les patients diagnostiqués avec un lymphome diffus à grandes cellules B (DLBCL) et traités par R-CHOP. En outre, l'amplification c-MYC est un facteur pronostique défavorable, amplifié par les réarrangements BCL2 et BCL6, respectivement, désignant les lymphomes de haut degré selon la révision de 2016 de l'OMS. Objectifs. Nous recherchons les corrélations de l'expression double ou triple des marqueurs c-MYC et