Proposed prognostic score including circulating free DNA concentration in diffuse large B-cell lymphoma

Non-Hodgkin’s lymphomas (NHLs) are common types of hematological malignancies. Due to the heterogeneity of the presentation of patients with diffuse large B‑cell lymphoma (DLBCL), multiple scoring systems are used to classify patients into different risk categories which impact the overall survival (OS) and progression-free survival (PFS). Circulating tumor DNA/circulating free DNA (ctDNA/cfDNA) is an emerging biomarker for lymphoma that can noninvasively provide genotypic information, monitor minimal residual disease, and monitor response. We aimed to discover the role of cfDNA concentration in the prognosis of DLBCL without using mutation-detecting techniques.

This prospective interventional nonrandomized open-label study was conducted with 36 individuals with NHL (DLBCL) who attended the Oncology Center Mansoura University (OCMU) from 2020–2021 with follow-up for 2 years. Basic laboratory and radiological investigations were done for all patients for diagnosis and staging. The ctDNA extraction was performed using the QIAamp DSP Virus Spin Kit, QIAGEN. Most of the patients were treated using the R‑CHOP (Rituximab, Doxorubicin, Cyclophosphamide, Oncovin, and oral Prednisolone) protocol. The study was approved by the Faculty of Medicine’s Ethical Committee (code number: MD.20.05.332).

The analysis resulted in identification of multiple factors significantly affecting the survival of DLBCL patients. Patient-related factors include old age (P = 0.051) and poor performance status (P = 0.05). Laboratory factors including high LDH (P = 0.0073), low serum albumin (P = 0.015), high absolute monocytic count (P = 0.05), BCL2 expression by Immunohistochemistry (IHC) (P = 0.058), high pretreatment cfDNA concentration (P = 0.032), and high posttreatment cfDNA concentration (P = 0.032) were significantly associated with an inferior OS. Based on the multivariate analysis, we proposed a prognostic score formed of pretreatment cfDNA plasma concentration (> 27 ng/ul), Lactate dehydrogenase (LDH) level (≥ 378 u/l), and serum albumin (< 3.8 g/dl) as independent risk factors. This score was applied to our cohort, each factor was given one point and the risk was classified based on the number of points: very low risk (0 points), low risk (1 point), intermediate risk (2 points), and high risk (3 points). When we applied this to our patients, higher scores were significantly associated with shorter OS (P = 0.00029).

We proposed a prognostic score showing a significant correlation with OS. The advantage of our score is that it is applicable and cost effective to be used when mutational analysis techniques are not available.