Intrathecal Administration of Rituximab for the Treatment of Primary Central Nervous System B-Cell Lymphoma.

Background: Patients with a primary central nervous system (CNS) lymphoma are very difficult to be treated. Regarding elderly patients, the side effects of the established strategies are considerable, particularly those caused by radiotherapy. Although with poor long term results, surgery, high dose chemotherapy and focal radiotherapy have been advised for these patients. Thus, new therapeutics strategies are needed. We report two cases of primary CNS B-cell lymphomas treated with rituximab intrathecally (ith). Case 1: In September 2003, a 59-year-old female with headache, paresthesia and weakness of the right limbs presented at our clinic. In August 2003 a brain biopsy of a parenchymal lesion was performed, vasculitis and cerebritis were found. The patient’s condition progressively worsened during the next 3 months and she developed a right-side hemiparesis. A PCR test to ascertain the presence of Mycobacterim tuberculosis in brain tissue was positive and rifampicin was prescribed. The patient presented at our clinic in September 2003, and in December 2003 she underwent another brain biopsy and CD20+ diffuse large B-cell lymphoma was diagnosed. Chemotherapy with high-dose methotrexate (MTX) 3.5 g/m² iv, MTX 12 mg ith and vincristine 1.4 mg/m² was scheduled every 15 days for a total of 5 cycles. The patient experienced a partial remission. In February 2004, rituximab 25 mg ith was administered on days 1–2 and days 8–9. There was no toxicity during, or after the rituximab infusions. In March, after a total dose of 200 mg, there was a complete radiological remission of the lymphoma and a consistent clinical improvement. In June 2004, the lymphoma relapsed, affecting the same area of the brain and in July 2004 a re-treatment protocol consisting of MTX 8g/m² and high dose cytarabine was started, without response. The patient died of sepsis, secondary to mucositis and pancytopenia in August 2004. Case 2: a 67-year-old male with a primary malignant B lymphoma CD20+ of the posterior fossa which relapsed after two surgeries, high dose chemotherapy and focal radiotherapy with lymphomatous meningitis. Complete remission was obtained after one course of high dose MTX (4g/m²) and intrathecal MTX, intercalated with three courses of systemic (350 mg/m²) and intrathecal rituximab (25mg/d - 8 days). The patient presented hepatotoxicity after the first dose of MTX iv. The relapse free survival is seven months until now and the patient is physically and intellectually fully recovered. No major side effects were observed with the administration of rituximab intrathecally.

Conclusion: Intrathecal administration of rituximab had no toxicity and was well-tolerated. Further studies are necessary to establish the best dose and schedule to achieve an improvement in the therapeutic response.