Recurrent primary central nervous system lymphoma complicated by lymphomatous meningitis

Primary central nervous system lymphomas (PCNSL) are chemosensitive primary brain tumors and are treated primarily with adjuvant chemotherapy. Nonetheless, therapy is palliative with the majority of tumors recurring in brain parenchyma. A common pattern of PCNSL recurrence is that of cerebrospinal fluid (CSF) dissemination manifested as lymphomatous meningitis (LM). Fourteen patients (8 men; 6 women) 34-76 years of age (median 56 years) with recurrent PCNSL manifested as either lymphomatous meningitis (8 patients) or combined parenchymal and CSF disseminated tumor (5) were retrospectively evaluated. All patients had received prior adjuvant therapy including surgery (gross total resection in 3; biopsy in 11), radiotherapy (whole brain in 11; craniospinal in 1; and orbital in 1) and chemotherapy (systemic in 13; intraventricular in 4). At recurrence, documented by either positive CSF cytology (14 patients) or neuroradiographic evidence of disease progression (6 patients), all patients were evaluated for extent of central nervous system disease. Two patients not previously irradiated were treated with whole brain radiotherapy. Eight patients received systemic chemotherapy including 7 patients (Brown University; Group A) treated with either high dose methotrexate (n=4) or cytosine arabinoside (n=3). Seven patients (UCSD: Group B) received intraventricular chemotherapy (methotrexate 5; cytosine arabinoside 4; thio-TEPA 4) without concomitant high dose systemic chemotherapy. Four of 14 patients (28.6%) are disease-free and have durable responses (median 36 months, range 22-56 months). Ten patients (71.4%) have died of disease progression (5 due to combined PCNSL and LM; 4 due to LM; and 1 due to PCNSL). Median survival was 5.5 months with a range of 3-12 months. Grade III/IV myelosuppression was seen in 5 patients, all as a result of systemic chemotherapy (Group A patients). Aseptic meningitis due to intraventricular chemotherapy was seen in 7 patients (Group B patients). No treatment-related deaths occurred. Four patients are disease-free and manifest leukoencephalopathy of whom 2 are symptomatic. Outcome was comparable in Group A and B patients. Recurrent PCNSL complicated by LM may be palliated by combined modality therapy and in this small series, approximately one-quarter of patients (two from each treatment group) are long-term survivors and disease-free. Outcome is similar in patients treated with intraventricular chemotherapy as compared to patients treated with high dose systemic methotrexate or cytosine arabinoside. Treatment-related toxicity was manageable however delayed neurotoxicity is seen in disease-free survivors.