Higher Incidence of Venous Thromboembolism Is Associated with Initial Cycles of Chemotherapy in Lymphoma Patients: Creatinine and Hemoglobin as Key Risk Factors.

Background: While Lymphoma patients are at increased risk of venous thromboembolism (VTE), the timing of VTE occurrence in reference to chemotherapy (CT) and risk factors are not well defined.

Methods: Medical records of all newly referred lymphoma patients (1046) to MD Anderson Cancer Center (MDACC) in 2003 were retrospectively reviewed over a follow-up period of two years for demographics, tumor histology, laboratory values, CT regimens, incidence of VTE, risk factors and management of VTE.

Results: Four hundred and twenty-two (422) out of 1046 patients received at least one cycle of CT at MDACC (total CT cycles 2126). The median age of the patients was 57 years (range, 17 to 87). Fifty eight % of pts were male and 62% were newly diagnosed. Seventy-three patients (17.3%) out of 422 had 80 new episodes of VTE; 58 deep vein thromboses (DVT) only, 17 pulmonary embolisms (PE) only, and 5 were combined DVT and PE. Only less than 5% (20/422) of pts received thromboprophylaxis during treatment for lymphoma. Interestingly, 68% (54/80) of episodes occurred by cycle 3 of CT suggesting that VTE episodes occurred primarily in patients with highest disease burden or during initiation of CT. Since the incidence was highest during the initial cycles of CT, we analyzed risk factors for the first regimen of CT. By multivariate logistic regression analysis, gender (female vs. male, OR=3.6, 95%CI 1.707 to 7.61, p=0.0008), high hemoglobin (OR=1.29, 95%CI 1.059 to 1.561, p =0.011), high serum creatinine (OR=3.36, 95%CI 1.372 to 8.228, p=0.0080), doxorubicin (DOX) and/or methotrexate (MTX)-based CT regimen (OR=2.948, 95%CI 1.352 to 6.429, p=0.0066) were found to be important risk factors for new VTE. Specifically, the estimated risk for lymphoma patients with baseline hemoglobin 12 gm/dL receiving DOX and/or MTX based CT with renal insufficiency (creatinine 2.0mg/dL) is 50% in females and 21% in males.

Conclusions: Lymphoma patients are at higher risk for VTE in the initial cycles of CT (cycles 1–3). Patients with high hemoglobin, elevated creatinine, female gender, and those receiving DOX and/or MTX based CT regimens are at higher risk for VTE than others. These clinically relevant findings suggest that a thromboprophylaxis strategy is needed in the patients presenting with these risk factors, particularly, in the initial cycles of chemotherapy.