Abstract

Diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease, but standard treatment is not effective enough for all patients. That is why so important to identify high risk patients who need more aggressive therapy at the time of diagnosis. Nowadays prognosis for patients with DLBCL is based on International prognostic index (IPI). However, this index consists of only clinical parameters and does not include the biological characteristics of the tumour. Immunohistochemistry (IHC) markers could also play a prognostic role. There are some publications regarding predictive and prognostic role of expression of Bcl-2, Bcl-6, MUM1, CD10 and CD30, but their results are controversial. The aim of our study was to analyze prognostic role of these markers, to compare survival of patients with positive and negative expression of these markers and to build a prognostic model which include biological parameters for identifying high risk patients. There were statistically significant differences in EFS between the group of patients with negative and positive expression of CD10 (51.5 % versus 72.5 %, р=0.01) and in OS between the group of patients with negative and positive expression of Bcl-6 (61.1 % versus 79.6 %, р=0.03). Six-factors nonlinear neural network prediction model (MLP_6) was built. The sensitivity of the model is 63.2 % (95 % CІ 49.3 % – 75.6 %), specificity – 85.2 % (95 % CІ 79.1 % – 90.1 %). Prognostic factors include negative IHC expression of Bcl-6, CD10, non-GCB molecular subtype (according to algorithm Hans), gender (male), advanced Ann-Arbor stages, >2extranodal involvement. Our nonlinear neural network prediction model could improve prognostic role of IPI by adding of biological tumour characteristics (IHC expression of CD10, Bcl-6, molecular subtype by IHC algorithm).

Highlights

  • Diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease, but approximately 40 % of patients are refractory to the primary therapy or develop relapse after first line therapy [1, 2]

  • Nowadays prognosis for patients with DLBCL is based on International prognostic index (IPI) [3]

  • Despite more numbers of high risk patients according IPI were in the group of patients with positive Bcl-2 expression, expression of this IHC marker did not have any influence on survival and did not show significant value during multivariable analysis

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Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease, but approximately 40 % of patients are refractory to the primary therapy or develop relapse after first line therapy [1, 2].Standard of treatment is not effective enough for this group of patients. Nowadays prognosis for patients with DLBCL is based on International prognostic index (IPI) [3]. IPI was described in1993 based on the analysis of 3273 patients with aggressive non-Hodgkin lymphoma in Oncologic centers, received CHOP-like treatment. Based on such negative prognostic factors as age more than 60 years old, elevated lactate dehydrohynase, status ECOG>1, ІІІ–ІV stages, extranodal sites of involvement >1, patients were divided into four risk groups: low (0–1 factor), low-intermediate (2 factors), high-intermediate (3 factors) and high risk (4–5 factors) with 5-year overall survival (OS) 73 %, 51 %, 43 % і 26 % [3]. There are some publications regarding predictive and prognostic role of expression of Bcl-2, Bcl-6, MUM1, CD10 and CD30, but their results are controversial

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