Assessment of the circulating cell-free DNA marker association with diagnosis and prognostic prediction in patients with lymphoma: a single-center experience

Abstract

Circulating cell-free DNA (ccfDNA) has been shown to be associated with the clinical characteristics and prognosis of cancer patients. Our objective was to assess whether the concentration and integrity index of ccfDNA in plasma may be useful for diagnosing and monitoring the progression of patients with lymphoma. We included plasma samples from 174 lymphoma patients and 80 healthy individuals. The total concentration of ccfDNA was determined using a fluorometry method, and the DNA integrity index (DII), which is the ratio of longer to shorter DNA fragments, for the APP gene was detected using real-time quantitative PCR. The median levels of the ccfDNA concentration and the DII in patients with lymphoma were significantly higher than those in controls (both P < 0.0001). Increases in the ccfDNA concentration and the DII were associated with advanced stage disease, elevated lactate dehydrogenase levels, and a higher prognosis score. In patients with diffuse large B cell lymphoma (DLBCL), high levels of ccfDNA (both concentration and the DII) showed an inferior 2-year progression-free survival (PFS) (P = 0.001; P < 0.0001, respectively). Our study provides quantitative and qualitative evidence in favor of using ccfDNA analysis in lymphoma patients for diagnostic and prognostic assessments.

Clinical significance of disease‐specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma

“…[19][20][21] However, this range of concentration was lower than that of cell-free DNAs in patients with systemic lymphomas (range 100-14 180 ng/mL). 22,23 In our analysis, the MYD88 L265P mutation was not detected in cell-free DNAs by TDS. However, Fontanilles et al recently reported that a variety of somatic mutations specific to CNS tumors, including MYD88 L265P mutation, were detected in cell-free DNAs of PCNSL patients by TDS.…”

“…Also, the estimated range appears to be higher than that of cell‐free DNA amounts in patients with non‐hematological neoplasms, such as colorectal, lung, and breast cancer (range 0.5‐1980 ng/mL) . However, this range of concentration was lower than that of cell‐free DNAs in patients with systemic lymphomas (range 100‐14 180 ng/mL) …”

The Impact of Pre-transplant Cell-free DNA Levels on Leukemia Relapse and Transplant-related Complications in Allogeneic Hematopoietic Stem Cell Transplant Recipients

“…Aside from several physiological states such as pregnancy and physical activity, pathological conditions, including inflammation and autoimmune diseases, may present with elevated cfDNA levels. In cancer, cfDNA levels may be increased up to 1000 ng/mL, which draws attention to an association between cfDNA levels and tumor burden (1,4,8,(10)(11)(12)(13). A previously reported association between age and cfDNA was confirmed in our study.…”

“…Cell-free DNA levels were elevated in various hematological disorders. High levels of cfDNA and DNA integrity index represented a lower probability of progression-free survival in diffuse large B cell lymphoma patients (8). Cell-free DNA levels were increased in lymphoma patients and correlated with advanced age and stage, poor prognosis, B symptoms, and lactate dehydrogenase levels (4,6,24).…”

“…In healthy individuals, cfDNA is a product of physiological hematopoietic cell cycle, including myeloid and lymphoid apoptotic cells, whereas in cancer patients, only a small amount of total cfDNA originates from neoplastic cells. The wide range of this circulating tumor DNA fraction, which differs between 0.01% and 60% of total cfDNA, depends on several tumoral features, including volume, stage, vascularization, proliferation, and apoptosis rate (1,2,4,(7)(8)(9). To date, the predictor role of cfDNA was demonstrated in a wide spectrum of malignancies, including hematological disorders such as AML, MDS, and lymphoid neoplasms (2).…”