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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. It is an heterogenous cancer that can have variable responses to therapy and profound differences in survival outcomes. DLBCL is of B- cell origin and was typically treated with a regimen of cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) but the addition of the anti-CD20 monoclonal antibody rituximab (R) significantly improved patient overall-survival (OS). A scoring system has been used to identify risk groups of DLBCL individuals called the International Prognostic Index (IPI) that uses age, lactate dehydrogenase levels, general health status, stage of tumor and number of disease sites to place the patients in 1 of 4 risk groups that correspond with the likelihood of 3-year OS. A revised IPI (R-IPI) using R-CHOP-treated patients was developed that had improved prognostic value at determining risk groups. What this historically used DLBCL scoring system lacks is more individualized data, including molecular information. Limited gene expression studies have been performed on DLBCL, which have successfully classified DLBCL subclasses. Here, we have expanded on previous gene expression studies and have identified genes that are associated with OS in DLBCL using data from the Lymphoma/Leukemia Molecular Profiling Project. Specifically, we have developed a prognostic gene signature consisting of 33 genes that, when transformed into a risk score, can stratify individuals into high or low risk groups that have significantly different OS. The prognostic gene signature was associated with OS in multiple clinical studies, and when used in conjunction with DLBCL molecular subtype and R-IPI score predicted OS with more accurately. Recently, we have developed a web based DLBCL Risk Score Calculator. This calculator combines our prognostic gene signature and the current R-IPI risk scoring system to generate risk scores and predict survival probabilities by year. Next, we will challenge our DLBCL Risk Score Calculator by performing RNA sequencing on DLBCL samples with documented pathology and progress reports. After validation, our DLBCL Risk Score Calculator will more accurately identify patients that will do well on standard care, and alert clinicians to patients that would benefit from experimental therapeutic approaches or more frequent clinical monitoring following treatment.
Khanal, Santosh; Gampala, Arjun; Geanes, Eric S.; Culpepper, Anne T.; Buryi, Liubomyr; Jackson, Catherine A.; McLennan, Rebecca; and Bradley, Todd, "Diffuse Large B-Cell Lymphoma Risk Score Calculator: A Tool To Accurately Predict Survival Risk And Improve Treatment Decisions And Outcomes" (2022). Research at Children's Mercy Month 2022. 12.