High Incidence of Venous Thromboembolism in Patients with Lymphoma Receiving Chemotherapy: Assessment of Risk Factors.

Background: Venous thromboembolism (VTE) is a significant cause of cancer morbidity and mortality. Lymphoma patients (pts) are at increased risk of VTE, however, the exact incidence and risk factors are unknown.

Methods: Of the 1050 newly referred Lymphoma pts to MDACC in 2003 identified, medical records (MR) of 538 consecutive pts were reviewed for demographics, tumor histology, staging, laboratory values, type of chemotherapy (CT) regimens, risk factors for VTE, incidence of VTE and management over a follow up of 2 years.

Results: 207 out of 538 pts received at least one cycle of CT at MDACC (total CT cycles 1125). The median age was 56 years (range 17–82); there were 81 females and 126 males. Majority of pts (61.8%) were newly diagnosed and the most common histologies were Large Cell Lymphoma (31.88%), followed by Hodgkin’s Disease (16.9%) and Follicular Lymphoma (14.98%). Thirteen out of 207 (6.28%) pts had history of VTE prior to CT and 37 (17.9 %) pts out of 207 had 41 new episodes of VTE; 29 Deep Vein Thrombosis (DVT) (12 upper and 12 lower extremity) and 12 Pulmonary Embolism (PE); 2 pts had both DVT and PE. All VTE episodes were confirmed by imaging except in 3 pts. The mean baseline hemoglobin (Hb) in VTE pts was 12.8 g/dL. The median cycle number for VTE occurrence was cycle 3 with 24/37 (64.86%) pts experiencing VTE by cycle 3 and 6/37 (16.2%) pts had VTE in cycle 1. Two out of the 37 (5.4%) pts had recurrent VTE. Among those with new VTE, 31/37 (83.78%) pts were of age greater than 40, 25/37 (67.56%) pts had BMI > 25, 32/37 (86.4%) pts had aggressive or highly aggressive histology and 29/37 (78.37%) pts had stage 3 or 4 disease. Twenty-three out of 31 (74.2%) pts had received erythropoietin before or during the cycle of VTE. Fourteen of 207 (6.79%) pts were on thromboprophylaxis before the chemotherapy. Only 1 of these 14 pts experienced VTE, approximately 2 months after the discontinuation of prophylaxis. Central venous catheter (CVC) thrombosis occurred in 6/174 (3.44%) patients with CVC. The most common systemic treatment for VTE was Enoxaparin (12/33). By multivariate logistic regression analysis of many of the previously described risk factors and other variables, Doxorubicin and/or Methotrexate based CT regimen was found to be a significant independent risk factor for VTE (OR 5.58, 95%CI 1.62 to 19.13. p = 0.0062).

Conclusion: VTE is a frequent and underestimated complication in Lymphoma pts. These findings underscore the importance of prospective clinical trials of anticoagulation prophylaxis in the high risk patients receiving CT.