A bio-clinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma.

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 serum LDH at relapse, and MYC or BCL2 protein or gene expression. A bio-clinical score using these 4 factors predicted outcome with 3-year event-free survival for cases with 0-1 vs 2-4 factors of 55% vs 16% (p<0.0001) respectively, for assessing MYC and BCL2 by immunohistochemistry, and 46% vs 5% (p<0.0001) assessing MYC and BCL2 mRNA by digital gene expression, and 42% vs 21% (p=0.079) assessing MYC and BCL2 by fluorescent in-situ hybridization. This proposed bio-clinical model should be furt...

Source: Haematologica - November 2, 2017 Category: Hematology Authors: Bosch M, Akhter A, Chen BE, Mansoor A, Lebrun D, Good D, Crump M, Shepherd L, Scott DW, Stewart DA, Canadian Cancer Trials Group Tags: Haematologica Source Type: research