Outpatients with Lymphoma on Chemotherapy: Specific Thromboembolic Risk Factors and Venous Thrombosis Incidence

INTRODUCTION: Incidence of venous thrombotic events (VTE) in patients with lymphomas is approximately 4%. There are a number of thrombotic risk factors (TRF) identified in this group of patients in general, like leukocytosis, dexamethasone, central nervous system lymphoma and primary mediastina large b-cell lymphoma and poor performance status. These TRF have not been evaluated specifically in patients with lymphoma under non-hospitalization chemotherapy regimen.

OBJETIVES:

• To evaluate the prevalence of general and specific TRF in patients with lymphomas under out hospital chemotherapy regimen in our center.

• To describe the incidence of thrombosis and ischemic events in this group of patients during treatment in our area.

• To describe the characteristics of vascular events.

• To evaluate the safety of antiplatelet and anticoagulant treatment during chemotherapy treatment in this group.

MATERIAL AND METHODS: This is a retrospective, one center study and single physician for the treatment and follow-up of patients. Patients with lymphoma diagnosed at our center and under out-hospitalization chemotherapy schemes of treatment, between January 2014 and December 2016, were included. We analyzed age at diagnosis, histology, stage, chemotherapy schemes, vascular events prior lymphoma diagnosis, antiplatelet or antithrombotic prophylaxis, use of erythropoietin, Hb<10g/dl, platelets (Plat)>350x109/L, leucocyte (LEU)>11x109/L, immobilization, Charlson, IMC >35, use of dexamethasone, doxorrubicine, radiotherapy, catheters and incidence and characteristics of vascular events. A descriptive analysis was performed, using absolute and relative frequencies for qualitative variables and measures of central tendency and dispersion for continuous variables. The study was carried out according to the Declaration of Helsinki and was approved by the Ethics Committee of the Regional University Hospital of Málaga.

RESULTS: We included 137 subjects, median age 54.3+/-18 years old, 51% of group were males. The most frequent types of lymphoma were diffuse large B-cell lymphoma (LDCGB) (30,6%), follicular Lymphoma (FL) (24,8%) and Hodgkin lymphoma (HL) (22,6%). Most of patients presented advance disease, 61,6% were stages III or IV, and 87.4% did not presented B symptoms. Schemes of treatment were R-CHOP or bortezomid-R-CHOP for LDCGB, R-Bendamustine or R-FC in FL and AVBD +/- radiotherapy in HL. Most of them got complete remission, 74,5% with only 17.5% con stable disease or progression. Median follow up of the serie was 20,3+/-16 months.

The 40,9% of patients had 3 or more TRF, incidence of each TRF: use of erythropoietin 4,4%, Hb<10g/dl 14%, platelets (Plat)>350x10⁹/L 19%, leucocyte (LEU)>11x10⁹/L 19%, immobilization 3,6%, Charlson 41%, IMC >35 2,9%, use of dexamethasone 5,1%, doxorrubicine 32,8%, radiotherapy 8%, catheters 3,6%.

Three patients (2,2%) patients presented VTE:

• Female 19 years old, EH 2B, plat>350x10⁹/L, Hb <10gr/L, leu 11x10⁹/L, doxorubicin. Upper limb thrombosis 22 months after diagnosis. Treatment LMWH 3 months.

• Patient 2: Female 74 years old, LDCGB 2A, plat>350x10⁹/L, Hb <10gr/L, charlson 4. Lower limb thrombosis 8 months after diagnosis. Treatment antivitamin-K 6 months.

• Patient 3: Male 40 years old, LDCGB 1A, plat>350x10⁹/L, doxorubicin. Upper limb thrombosis 8 months after lymphoma. Treatment LMWH 3 months.

Three patients were under secondary antiplatelet prophylaxis for prior arterial ischemia. One of them presented a gastrointestinal bleeding after 8 months under chemotherapy and concomitant antiplatelet secondary prophylaxis. Of the 3 patients who develop VTE events after lymphoma diagnosis, one presented an upper gastrointestinal bleed, 20 days after anticoagulation started. Coagulation test were normal and Platelets number higher than 100x10⁹/L at bleeding event. According to these data, 2 of 6 patients under chemotherapy and antiplatelet o anticoagulant treatment presented grade 3 bleedings (30%).

CONCLUSIONS: Prevalence of VTE in patients with outpatient with lymphoma looks lower than global lymphoma. Three VTE affected patients presented 3 or more TRF. Upper limb thrombosis was the most frequent one, probably related with the local administration of chemotherapy. Bleeding risk in patients with chemotherapy treatment and concomitant antiplatelet or anticoagulant drugs has to be carefully evaluated.