Favorable Treatment Alternative for Primary Central Nervous System Lymphoma: Combined Chemotherapy Regimen Consisting of High-Dose Methotrexate, Rituximab and Cytosine-Arabinoside

Introduction: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma that is limited to the brain parenchyma, intraocular compartment, cranial nerves, leptomeninges and spinal cord. New treatment strategies have improved prognosis.

Methods: We present 10 PCNSL patients diagnosed at Ankara University Department of Hematology between 2006 and 2014 and treated at both Ankara University Department of Hematology and Ankara Medicana Hospital. Survival data was analyzed using Kaplan Meier method and Log-Rank.

Results: Five of the 10 patients were male. The average age of the group was 53.40 ± 14.45 years (range: 29-72 years); the average age was 60 ± 9.8 years (range: 48-72) for the female patients and 46.8 ± 16.2 years (range: 29-67) for the male patients. The patients’ performance statuses based on Eastern Cooperative Oncology Group (ECOG) scores were distributed as follows: score 0, 2 patients; score 1, 5 patients; score 2, 1 patient; and score 3, 2 patients. The most common symptoms at diagnosis was headache in 6 patients followed by dizziness in 2 patients, memory loss in 1 patient and lumbar pain in 1 patient. Diagnoses were established by craniotomy in 5 patients, stereotactic biopsy in 4 patients and cerebro-spinal fluid analysis in 1 patient. Four patients had total resection, and 1 patient had debulking surgery after diagnosis. The cerebral/spinal parenchyma was involved in 5 patients, whereas 5 patients exhibited deep brain involvement. Eight patients had brain edema, whereas 7 patients had mass effect. Multiple lesions were detected in 7 patients. The mean serum lactate dehydrogenase level was 354 U/L (range 102-555). All of our patients were HIV and EBV negative. Eight patients were treated every 28 days with rituximab (R; 375 mg/m2/day) on the first day, methotrexate (MTX; 3.5 gr/m2/day) and cytosine-arabinoside (ARA-C; 4.4 gr/m2/day) on the second day and ARA-C (4.4 gr/m2/day) on the third day. Of the 8 patients, 3 patients received 4 cycles. One patient received 3 cycles and displayed a complete remission response. This patient received autologous hematopoietic stem cell transplantation (AHSCT) with cyclophosphamide (4x1.5 g/m2), etoposide (4x250-400 mg/m2) and carmustine (4x150-200 mg/m2) conditioning regimen as consolidation treatment. One patient received 2 courses of R-MTX-ARA-C and exhibited progressive disease; AHSCT was applied. All 5 patients ultimately experienced complete remission. The remaining 3 patients are still in their first and second courses of R-MTX-ARA-C -with a successful outcome in interim analysis-. Two of the initial 10 patients had high ECOG performance scores, received 1 course of MTX and radiotherapy (RT; 36-45 Gy) and died. The median overall survival (OS) in the R-MTX-ARA-C group was 18.3 ± 8.5 months, whereas the OS was 4.5 ± 2.1 months in the MTX-RT group (p<0.05). The event-free survival (EFS) was 12 ± 6.3 months in the R-MTX-ARA-C group and 1.5 ± 0.7 months in the MTX-RT group (p<0.05).

Conclusion: R-MTX-ARA-C -followed by AHSCT- can serve as a favorable treatment alternative in highly aggressive lymphoma like PCNSL.