Inflammatory response may indicate risk for venous thromboembolism in lymphoma subtype

An increase in the absolute neutrophil count/absolute lymphocyte count ratio may indicate increased risk for VTE in patients with diffuse large B-cell lymphoma, according to findings presented at the ASH Annual Meeting and Exposition.

In addition to this ratio, which measures systemic inflammatory response, the presence of certain clinical factors may contribute to VTE risk in these patients.

VTE is a “frequent complication” of DLBCL that is associated with a poor prognosis, according to Jahnavi Gollamudi, MD, a hematology/oncology fellow in the department of medicine at University Hospitals Cleveland Medical Center, and colleagues. Prior research demonstrates that anthracyclines, advanced disease at the time of presentation, obesity and the occurrence of neutropenia and anemia following the first cycle of chemotherapy are risk factors for the development of VTE.

In addition, “recent studies suggest leukocyte subpopulations may affect the risk of VTE,” Gollamudi and colleagues wrote. “Elevated neutrophil and monocyte counts have been associated with increased risk [for] VTE in solid malignancy. The role of leukocyte subpopulations in VTE risk in DLBCL has not yet been evaluated. We conducted a retrospective study to identify risk factors for VTE and specifically address the role of leukocytes and their subtypes in VTE risk assessment in DLBCL.”

The researchers obtained data for 542 patients diagnosed with DLBCL between 2000 and 2016 from the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center. Information on patient characteristics was recorded at baseline.

The median age of patients was 64 years (range, 16 to 92 years); 40.2% were aged 60 years and older. Slightly more than half of the participants were men (54%; n = 292). B symptoms were reported in 182 patients (35.8%). The median absolute neutrophil count was 4.6 x 10⁹/L (range, 0.39 to 36.9 x 10⁹/L) and the median absolute lymphocyte count was 1.23 x 10⁹/L (range, 0.05 to 13.5 x 10⁹/L).

The researchers also examined patient records for information on VTE, including radiographic confirmation.

Over a median follow-up period of 48 months, VTE occurred in 93 patients. The 1-year and 2-year cumulative occurrence of VTE was 13.5% (95% CI, 10.9% to 16.8%) and 20.5% (95% CI, 17.3% to 24.3%), respectively. In the following years, risk for VTE increased “more modestly,” according to the study results, reaching 23.6% at 4 years (95% CI, 20.2% to 27.7%). The majority of VTE events (80%) were observed in patients with active disease.

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More than half of VTE events observed (53%) were lower-extremity deep vein thrombosis. Other events included upper-extremity deep vein thrombosis (31%) and pulmonary embolism (16%).

Risk factors associated with statistically significant odds for greater hazard of VTE on univariate analysis included prior VTE, an albumin level of less than 3 gm/dL, a leukocyte count above 11,000/mcL, a hemoglobin level of less than 12 gm/dL, an absolute neutrophil count, an absolute neutrophil count to absolute lymphocyte count ratio above 2.5 and the incidence of bulky disease at diagnosis. A BMI greater than 35 kg/m², bulky disease and an absolute neutrophil count to absolute lymphocyte count ratio equal to or greater than 2.5 persisted as statistically significant risk factors for VTE in multivariate analysis.

The incidence of VTE at any point after DLBCL diagnosis correlated with poorer OS and PFS. Projected 4-year OS in patients diagnosed with VTE was 50.6% (95% CI, 39.7% to 61.6%) compared with 71.3% (95% CI, 66.9% to 75.7%; P < .0001) in patients who did not develop VTE. Projected 4-year PFS in patients diagnosed with VTE was 37.5% (95% CI, 27.1% to 48%) and 60% (95% CI, 55.3% to 64.7%; P < .0001) in patients who did not develop VTE.

“The first 24 months after DLBCL diagnosis appear to be the time of highest VTE risk, likely a consequence of active disease, treatment and other risk factors such as indwelling catheters,” the researchers wrote. “Leukocyte subpopulations appear to have a correlation with VTE risk; the absolute neutrophil count to absolute lymphocyte count ratio is a measure of systemic inflammatory response and, in DLBCL patients, a ratio above 2.5 is correlated with increased risk of VTE. Incorporation of this laboratory measurement to currently available VTE risk assessment tools may help more precisely identify [patients] at highest risk of VTE.” - by Julia Ernst, MS

Reference:

Gollamudi J, et al. Abstract 495. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosures: Gollamudi reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.