The International Prognostic Index Is a Better Predictor of Thrombotic Complications Than the Khorana Score for Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Results of a Single Center Prospective Cohort Study

Thrombotic complication is a major life threatening condition in lymphoma patients because chemotherapy as well as lymphoma cell itself can result in thrombosis. Although high rates of thrombotic complication have been reported in patients with lymphoma, the majority of data were from retrospective studies with heterogeneous group of patients. Furthermore, the frequency of thrombotic complications varied depending o the nature of studies and subtypes of lymphoma included. Thus, it is still not determined about the risk factors for thrombotic complications in lymphoma patients. As a predictive model for cancer-associated thrombosis, Khorana risk score has been proposed including cancer type, body mass index (BMI), prechemotherapy white blood cell, hemoglobin, and platelet count. However, there is few data prospectively validating the role of this risk model in Asian lymphoma patients. Therefore, we explored risk factors influencing the occurrence of venous and arterial thrombotic complications in diffuse large B-cell lymphoma (DLBCL) patients who were uniformly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

We analyzed the incidence of venous and arterial thrombotic complications from DLBCL patients enrolled in our prospective cohort study (NCT00822731). Patients were pathologically confirmed and treated with R-CHOP. Thrombotic complications defined as venous thrombosis including pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT), and arterial thrombosis including stroke and infarction occurred after diagnosis. The thrombotic complications were diagnosed with radiologic imaging studies including CT scan and ultrasound imaging.

352 patients were enrolled between 2008 and 2011, and they were prospectively monitored regarding the occurrence of thrombotic complications with the median follow-up duration of 22. 6 months. The median age was 56 years old (range 16–86) and male to female ratio was 1. 3:1. Thrombotic complications occurred in 48 patients (crude incidence: 13. 6%) including venous thrombosis (n = 37, 10. 5%) and arterial thrombosis (n = 11, 3. 1%). Venous thrombosis including DVT and PE occurred within 6 months after diagnosis (32/37, 86. 5%), so the actuarial incidence of venous thrombosis at one year was 10. 1%. However, arterial thrombosis mainly occurred around 12 months after diagnosis. Among 37 cases of venous thrombosis, anticoagulation therapy was used for 22 patients with symptomatic DVT or PE. Incidental cases of DVT or PE which were found during imaging follow-up for evaluation of tumor response did not require therapy. There were two deaths-related with venous thrombosis including refractory hypoxemia due to PE and bleeding due to anticoagulation while no death was found in arterial thrombosis. Age older 60 years and poor performance status (≥ ECOG grade 2) were significantly associated with thrombotic complications. However, other host factors including co-morbidity, body mass index (BMI), and gender were not related (P > 0. 05). Disease-related factors representing high tumor burden such as elevated serum LDH, two or more than two extranodal involvements, and Ann Arbor stage III/IV were significantly associated with increased risk of thrombotic complications (P < 0. 05). However, a particular extranodal site including stomach, pancreas, intestine, and mediastinum did not influence the thrombotic complications. Khorana score-based risk model failed to predict the occurrence of thrombotic complications in our study population. Furthermore, each parameter such as the level of hemoglobin, white blood cell and platlet count before chemotherapy, and BMI did not show a significant association with venous and arterial thrombotic complications. In fact, the number of patient more than 35 kg/m2 BMI was extremely small in our population. As a result, the International Prognostic Index was predictive for the occurrence of thrombotic complications in diffuse large B-cell lymphoma patients treated with R-CHOP.

The incidence of venous and arterial thrombotic complications in our study population was significantly associated with the IPI rather than Khorana score model. These results may help better defining lymphoma patients at high risk of thrombotic complications in Asian lymphoma patients.

No relevant conflicts of interest to declare.