[Therapeutic management of central nervous system lymphomas in a single hematological institute]

Primary central nervous system lymphoma is defined as an extranodal lymphoma arising in the central nervous system in the absence of systemic disease. Because of their rare occurrence among lymphomas, optimal treatment could hardly be established.

In this retrospective survey we analyzed the result of combined treatment (systemic and intrathecal chemotherapy followed by consolidation radiotherapy) in patients with primary or relapsed central nervous system lymphomas diagnosed and treated in our hematological department between 1998-2009.

During this period (mean follow-up of 13.2 months) from 427 patients with newly diagnosed non-Hodgkin's lymphomas, 22 primary central nervous system lymphoma was diagnosed (5.15%, 16 cerebral and 6 spinal cord lymphoma cases). Significant male predominance (14:8) was registered with an age distribution of 34-77 years (mean = 60.7, median = 64 years). No patients were immunocompromised. All central nervous system lymphoma specimens taken with neurosurgical resection or stereotaxic biopsies were confirmed histopathologically. All cerebral lymphoma cases proved to be diffuse large B-cell of origin, while in epidural lymphomas low grade subtypes also occurred. Epidural lymphomas were treated with local radiotherapy (30-40 Gy), except for patients with follicular lymphomas getting rituximab-containing polychemotherapy (R + CHOP regimen) before irradiation. In cerebral lymphoma (every patients had supratentorial localization) the following combined therapy protocol was used: up to three courses of high dose methotrexate (HD MTX 3g/m 2 in a single dose for 4 hours lasting drop-infusion) were given at 4-week intervals, followed by leucovorin-rescue 24 hours after MTX infusion. Intrathecal combination of methotrexate, cytosin-arabinosid and dexamethasone was given three times after HD MTX infusion. In complete response after chemotherapy (evaluated by cranial MRI or CT, PET/CT), whole-brain irradiation was used in a total dose of 30 Gy. In case of partial response, boost irradiation for the tumor bed was also given. In relapse or resistant cases, salvage regimen was applied: HD MTX course combined with high dose cytosin-arabinosid (HD Ara-C) 3g/m 2 /dose b.i.d. over 4 h c.i., repeated in three cycles every four weeks.

Complete remission has been achieved in 9 patients with cerebral and in 4 patients with spinal cord lymphoma (13/22; 59.0%), however, one relapsed patient became resistant and later expired, despite salvage therapy. Primarily 9 patients were not evaluable for response: 5 received only one or two HD MTX because of side effects, 4 patients died due to progression of the disease. Mean of the overall survival (OS) in cerebral lymphoma was 19.5 (3-46, median of 10) months, in epidural group 14.1 (2-76, median of 5) months, whilst mean time to progression (TTP) was 4.5 (2-6.5, median of 4 months). The 2-year survival for all patients was 50%. Acute toxicity of chemotherapy was usually hematological, moreover, in 8 patients impaired renal function and sepsis developed. No serious adverse effect of radiotherapy could be detected.

In primary central nervous system lymphoma, basic treatment HD methotrexate together with intrathecal combination of methotrexate + cytosin-arabinosid + dexamethasone followed by whole-brain irradiation of at least 30 Gy could produce a medium response rate in our study. In case of relapse or progression, other salvage regimens containing HD Ara-C alternating with HD MTX could reduce the treatment failure, as well. After therapy PET/CT was negative in five patients with prolonged disease-free survival.