Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas

Abstract

Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs. Data for VTE occurrence were retrieved from study databases and pharmacovigilance reports. Our analysis includes 1717 patients from 12 prospective phase II and III trials, including newly diagnosed NHL. We observed 53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The cumulative incidences for "all-grade" or grade ≥3 VTEs were 2.9 % (95 % CI: 2.1-3.8) and 1.1 % (95 % CI: 0.6-1.6), respectively. KS categories were positively associated with the risk of VTE of any grade, and with severe events (i. e. grade ≥3; Gray's test p-values = 0.048 and 0.012, respectively). Among NHL patients, those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any grade) VTE (HR: 3.42, 95 % CI: 1.32-8.84, p-value = 0.011). Our study indicates that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of VTE events and 3) DLBCL histotype is an independent risk factor for VTE incidence, for which preventative interventions could be considered.

Risk factors for venous thromboembolism in patients with lymphoma requiring hospitalization

“…Patients as those with low-grade histology who did not require a hospital stay were not retrieved. As expected, this may explain the higher incidence rate of VTE with respect to other reports 1,2,8,10 . Therefore, our study tackles the issue of VTE frequency in a population at increased risk, in whom special care is required and specific information are needed.…”

“…Comparison with other studies 8,10 is difficult because of differences in patient selection. Our study cohort is a real-life case series including both HL and NHL, including also VTE that was present before the start of therapy.…”

“…Khorana et al developed a risk model for predicting chemotherapy-associated VTE based on baseline clinical and laboratory variables; however, only a minority of patients (12.6%) in the study cohort had lymphomas 1 . Several studies indicate a higher VTE risk in patients with aggressive non-Hodgkin lymphomas (NHL) 2,4–8 , advanced stage disease (III/IV) 2 , localization in the central nervous system (CNS) 9 , and use of anthracyclines 2 . The incidence of VTE during chemotherapy in NHL patients was investigated analyzing the databases of 12 Italian clinical trials, identifying DLBCL histology and Khorana score as risk factors 8 .…”

“…Several studies indicate a higher VTE risk in patients with aggressive non-Hodgkin lymphomas (NHL) 2,4–8 , advanced stage disease (III/IV) 2 , localization in the central nervous system (CNS) 9 , and use of anthracyclines 2 . The incidence of VTE during chemotherapy in NHL patients was investigated analyzing the databases of 12 Italian clinical trials, identifying DLBCL histology and Khorana score as risk factors 8 . A recent monocentric study identified mediastinal involvement, BMI > 30 kg/m 2 , reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100 g/L as VTE risk factors in patients who had received at least one chemotherapy cycle 10 .…”

Venous thromboembolism in primary central nervous system lymphoma during frontline chemoimmunotherapy

“…Two retrospective reviews of patients with PCNSL treated with HD-MTX-based regimens who received routine inpatient prophylactic anticoagulation found a similar VTE incidence to our observed rates, and VTE episodes all occurred within two cycles of HD-MTX chemotherapy. 17,18 As in previous studies, KRS was found to predict risk of VTE in lymphoma, 15 and we hypothesized that it could also be useful in PCNSL. Adjustment of risk categories, labeling KRS ≥ 2 as "high risk" rather than KRS ≥ 3, may be required.…”