Low Molecular Weight Heparin (LMWH) for Venous Thromboembolism (VTE) Prophylaxis in Patients with Primary Central Nervous System Lymphoma (PCNSL)

Introduction: Venous thromboembolism (VTE) is a frequent, potentially lethal, complication in patients with cancer. Patients with brain tumors are at a particularly high risk for VTE. Primary central nervous system lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma, involving the cranio-spinal axis. The incidence of VTE in patients with PCNSL is as high as 30-60% in various series, occurring mostly in the early period of therapy. Due to this high incidence, the policy in our medical center since the year 2005, is to treat with prophylactic low molecular weight heparin (LMWH) from the time of PCNSL diagnosis until the end of treatment. We aimed to evaluate the incidence of VTE in patients with PCNSL treated with prophylactic LMWH.

Material and methods: All patients ≥18 years who were diagnosed and treated for PCNSL in Hadassah-Hebrew University Medical Center between the years 2005-2017 were included in the study. We retrospectively reviewed their medical records for demographic details and initial disease characteristics (age at diagnosis, sex, performance status, laboratory results such as LDH, cerebrospinal fluid content and location of the growth), for details of risk factors for VTE such as diabetes, smoking or heart failure, and for personal or familial history of thrombosis. Therapeutic details including chemotherapy protocol, response to treatment and supportive care were compiled. Specifically we noted if prophylactic LMWH was given, if any complications developed due to the LMWH treatment and whether a VTE event occurred.

Results: Forty four patients were included in the study. Mean age at diagnosis was 60.2 years and there were 27 (61%) females. Three (6.8%) patients had a personal history of thrombosis and 13 (29%) had a history of diabetes or smoking. Thirty two (72%) had an ECOG performance study of 0-1 at diagnosis and seven (16%) had leptomeningeal involvement. Forty one (93%) of patients were treated with a systemic high dose methotrexate (HDMTX) based protocol (mean of 7.6 courses of HDMTX per patient) and thirty two (73%) patients were treated with systemic rituximab. All 44 patients were treated with prophylactic LMWH, mostly at a dose of 40 mg per day (41 patients, 93%). Of the 44 patients, five (11%) discontinued treatment; 2 due to side effects (abnormal liver function tests and subdural hematoma (SDH)) and 3 for an unknown reason. Three (7%) patients had a minor bleeding event (gum, conjunctival, Ommaya reservoir catheter tract). One patient (2.3%) had a major bleeding event (SDH) while on LMWH treatment which was found on routine MRI imaging of the brain as he was asymptomatic. No VTE events (0%) were recorded in patients treated with LMWH. Two patients had a VTE, however both patients were off LMWH treatment at the time of VTE (one stopped LMWH, the other was diagnosed with VTE concurrently with the diagnosis of PCNSL).

Conclusions: In our group of 44 PCNSL patients, prophylactic use of LMWH was highly effective, with no VTE events. Two cases of VTE occurred in our patient group, both occurred while the patients were off LMWH treatment. Only one, asymptomatic, intracranial bleed was recorded, indicating the relative safety of this treatment in PCNSL patients. Further prospective studies should be done to support the routine use of this prophylactic strategy.