CNS Lymphoma and Thrombosis

Abstract & Commentary

Synopsis: Although a high incidence of thrombotic events is reported for primary brain tumors, the incidence in patients with CNS lymphoma is previously unreported. In a retrospective review from a single institution, 25 of 42 patients with CNS lymphoma experienced venous thromboembolism, and in 3 cases the event was fatal. Although the data now available are retrospective and from a single institution, a case for prophylactic anticoagulation is made, particularly during the treatment phase of this disorder.

Source: Goldschmidt N, et al. Cancer. 2003;98: 1239-1242.

Venous thrombosis occurs commonly in patients with malignancy, perhaps as often as in 15% of patients. Patients with glioblastomas and other primary brain tumors are at particularly increased risk. Goldschmidt and colleagues at the Hadassah-Hebrew University Hospital in Jerusalem performed a retrospective analysis of 42 patients with CNS lymphoma treated at their center to determine the risk of venous thrombosis in patients with this tumor type. Of the 42 CNS lymphoma patients seen between 1992 and 2001, 25 patients (59.5%) had venous thrombosis, and 3 patients (7%) died of overwhelming pulmonary embolus. Fourteen of the 25 patients had DVT of lower extremities, and 11 patients had pulmonary emboli, 5 of whom had no demonstrable DVT.

The majority of the DVT events occurred during the early period of treatment. Goldschmidt and colleagues suggest that anticoagulation be provided to prevent DVT in patients with CNS lymphoma.

Comment by William B. Ershler, MD

The incidence of thromboembolism is notable in patients with cancer in general, but is particularly prominent in patients with both primary brain tumors and lymphomas. In patients with brain tumors, the occurrence in some series is as high as 28%.1 Risk factors include leg paresis, a histological diagnosis of glioblastoma multiforme, age 60 years or older, large tumor size, the use of chemotherapy, and length of surgery of > 4 hours.2 In patients with lymphoma, the incidence of thromboembolism ranges between 6.6% and 13.3%,3,4 and in many cases it has been attributed to venous obstruction by bulky lymphadenopathy or to indwelling venous catheters. In the current series of CNS lymphoma patients, the incidence was considerably higher—nearly 60%. Goldschmidt et al speculate that the reason for the higher incidence relates to the risks associated with CNS disease, as well as certain hypercoagulable factors observed in patients with lymphoma. Furthermore, patients in their series were subjected to intensive chemotherapy regimens, and it was noted that thromboembolism in the great majority of cases occurred within several weeks of the start of chemotherapy. Chemotherapy has been shown to induce a hypercoagulable state by reducing levels of protein C and S5 and antithrombin III.6 Furthermore, methotrexate and carboplatin (one or the other was used in the majority in this series) can enhance the thrombogenic tendency by elevating levels of homocysteine or von Willebrand factor, respectively.4,7

Thus, this series, albeit from a single institution and subject to all the concerns of a retrospective analysis, is likely to accurately reflect a high incidence of thrombotic events in patients with CNS lymphoma. It is tempting to conclude that all such patients should be anticoagulated, at least during the time they are receiving intensive chemotherapy. To strengthen this argument, the same group of investigators has embarked upon a prospective study using low-molecular-weight heparin in all patients with CNS lymphoma. Their very preliminary results, mentioned in the Discussion section of the current report, indicate that there have been no thrombotic events and no hemorrhagic complications among the first 10 patients at a median duration of 14 months. Hopefully, the report of this study will be available soon. In the meantime, clinicians should consider the impressive findings from this 1 retrospective review and consider anticoagulation in patients with CNS lymphoma.

Dr. Ershler is INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.

References

1. Quevedo JF, et al. Mayo Clin Proc. 1994;69:329-332.

2. Marras LC, et al. Cancer. 2000;89:640-646.

3. Ottinger H, et al. Eur J Hematol. 1995;54:186-194.

4. Clarke CS, et al. Cancer. 1990;66:2027-2030.

5. Slhebak AA, Smith DB. Cancer Chemother Pharmacol. 1997;39:462-466.

6. Haire WD. Semin Hematol. 1995;32:56-60.

7. Weijl NI, et al. J Clin Oncol. 2000;18:2169-2178.