Central nervous system relapse of systemic non-Hodgkin's lymphoma: results of treatment based on high-dose methotrexate combination chemotherapy

The objective of this study was to evaluate the feasibility and possible response to pre-radiation chemotherapy given to patients with central nervous system (CNS) relapse of systemic non-Hodgkin's lymphoma (NHL). Twenty-three consecutive adult patients with systenic NHL and first CNS relapse were evaluated by CSF cytology and neuroaxis MRI. Treatment was based on weekly high-dose methotrexate (HD-MTX) 3.5 g/m2 and weekly intra-CSF cytarabine (ARA-C). Oral procarbazine 100 mg/m2 days 2-15 was added to patients whose bone marrow reserve could tolerate this drug. Radiation therapy (RT) to the CNS was deferred in responding/stable CNS disease. All patients with leptomeningeal seeding, but without parenchymal involvement responded to treatment prior to RT with 33% achieving a complete response (CR). Concomitant response of systemic disease was noted in 36% of the cases with 9% CR. Addition of RT to the CNS did not significantly change the overall rate of CR. Progression free survival for CNS disease was 5 months and for systemic disease 2 months. All patients with parenchymal involvement responded to therapy prior to RT with only 9% achieving CR, and the addition of RT in these cases increased the rate of CR to 24%. In this group, three of four patients who had active systemic disease responded systemically. Progression free survival was 3 months for both CNS and systemic disease. The median survival of the whole group was 6 months; 1-year survival 32% and 2-year survival 15%. In conclusion, systemic HD-MTX-based combination chemotherapy yields an initial response rate of 100% in the CNS and a 47% concomitant systemic response. A complete CNS response can be obtained prior to RT but this adds little to the overall CR rate. Durable responses are rare. Since both CNS and systemic relapses appear in tandem, future trials should evaluate alternative modalities in order to enhance drug delivery into the CNS.