Primary polychemotherapy based on high-dose methotrexate (MTX) and cytarabine (Ara-C) is highly efficient in treatment of primary central nervous system lymphoma. About half of patients 60 years or younger can obviously be cured with this regimen without long-term neurotoxic sequelae or quality-of-life compromise.

and 5) and cytarabine (Ara-C; cycles 3,6) based systemic therapy including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide.Results: Study accrual was prematurely stopped in 11/05 due to a high rate of early relapses.Seventeen/18 patients were assessable for response: Nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu), two (12%) partial response (PR), four (24%) showed progressive disease (PD); one treatment was stopped due to toxicity.Median follow-up is 23 months; median response duration was only ten months in responding patients and median time to treatment failure (TTF) eight months in the whole group; median overall survival (OS) has not been reached. Systemic toxicity was mainly hematologic.Conclusions: In PCNSL patients < 60 years polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with intraventricular treatment.

In patients with primary CNS lymphoma (PCNSL) treated with a methotrexate (MTX)-based chemotherapy, no gross cognitive decline has to be expected as a long-term treatment effect. MTX-induced white matter changes apparent on MRI are not inevitably associated with cognitive impairment. Nevertheless, a substantial fraction of patients with PCNSL retain cognitive deficits as a residual symptom of the tumor.

In primary central nervous system lymphoma (PCNSL), 2 international prognostic scores have been developed to estimate the outcome according to certain "prognostic groups". However, these scores do not predict the individual course of a single patient under therapy. In this analysis, we addressed the question of whether early tumor remission in patients still under therapy, according to magnetic resonance imaging (MRI) criteria, helps to predict long-term outcome. Eighty-eight patients treated with 6 polychemotherapy cycles within a pilot/phase II trial underwent MRI scanning within 72 hours prior to initiation of therapy, after the second chemotherapy cycle, and after completion of chemotherapy. Response was assessed by contrast-enhanced MRI of the brain according to the Macdonald criteria. Median follow-up was 42 months (range, 0-124 months). Patients achieving a complete radiographic response after 2 courses of chemotherapy (n = 18) had a significantly longer median overall survival (OS) (not reached) and median time-to-treatment failure (TTF) (not reached) than patients with complete response (CR) after termination of treatment but with only a partial response after the second cycle (n = 24) (OS: 55 months; TTF: 32 months) (P < .01). Early complete tumor response assessed by MRI after the second of sixth scheduled chemotherapy cycles was highly predictive for both OS and TTF in patients with PCNSL treated in this series.

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Background: Treatment of primary CNS lymphoma (PCNSL) with a combined systemic and intraventricular chemotherapy (Bonn protocol) has achieved an overall response rate (ORR) of 84% and long term complete remissions in a substantial fraction of patients younger than 60 years. Purpose: Due to a high infection rate of the Ommaya reservoir the question was addressed if intraventricular treatment is dispensable in this polychemotherapy protocol. Patients and Methods: Fifty patients with histologically confirmed PCNSL were enrolled onto a phase II-study evaluating chemotherapy without radiotherapy and without intraventricular treatment. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was administered. Results: In an ongoing trial thirty-five of 50 patients (18 pat. < 60 years, 17 pat. over 60 years) are yet assessable for response after a median follow up of nine months (range: 1 to 26 months). In 18 patients < 60 years, the ORR was 78%. However, median time to treatment failure (TTF) was eight months, and median progression free survival (PFS) only 7 months according to frequent early relapses. Conclusions: Early relapses are frequent in younger patients treated with the modified Bonn protocol without intraventricular treatment despite a high ORR. These preliminary results support the assumption that intraventricular treatment is essential to achieve sustained remissions after successful treatment of PCNSL.