Impact of meningeal dissemination (MD) on outcome in primary CNS lymphoma in the G-PCNSL-SG1 trial

Abstract

Background: The prognostic impact of MD in PCNSL is still debated. Within the framework of a multicenter randomized trial (G-PCNSL-SG1) we evaluated patients for outcome according to the presence of MD. Methods: Immunocompetent adult patients were initially treated with up to six cycles of high-dose methotrexate (HD-MTX; 4g/m 2) based chemotherapy without intrathecal therapy. Those randomized to radiotherapy subsequently received whole-brain radiotherapy (WBRT) with 45 Gy, in 1.5 Gy fractions; those randomized to chemotherapy did not receive further therapy in case of complete remission or highdose cytarabine when complete response was not achieved. MD was defined by the presence of lymphoma cells in the cerebrospinal fluid (CSF) detected by at least one of the following methods: cytomorphology, detection of clonal B cells by polymerase chain reaction of rearranged immunoglobulin heavy-chain genes (IgH-PCR) or contrast enhancement of the leptomeninges on MRI. Results: All 526 patients fulfilling the eligibility criteria were entered into the analysis. MD at presentation was detected in 104 (19.8 %) patients: 95 by cytomorphology, 16 by PCR and 17 by MRI. Pretherapeutic characteristics including age, Karnofsky performance score, sex, serum lactate dehydrogenase, lymphoma localization, mode of biopsy, histology, CSF protein elevation (>45mg/dl) and ocular involvement did not significantly differ in patients with MD and other patients (all p>0.05). Only CSF pleocytosis (>5/ll) was significantly more frequent in patients with MD (37 vs. 14%, p<0.001). The type of chemotherapy (HD-MTX: 83 vs. 75%, HD-MTX and ifosfamide: 17 vs. 25%) applied and the frequency of WBRT (39 vs. 34%) were not significantly different in the group with and without MD. Median overall survival (OAS) in the MD group was 21.5 (95% CI 17.1-25.8) months as compared to 22.4 (17.3-27.5) months in other patients (p=0.8); median progression free survival (PFS) was 6.1 (1.6-10.5) and 7.0 (5.2-8.8) months, respectively (p=0.9). Median OAS and PFS were not significantly different in patients with elevated CSF protein or CSF pleocytosis compared to patients with normal CSF values. Conclusion: MD, elevated CSF protein and CSF pleocytosis had no impact on outcome in this trial.

Neuro-oncology: a selected review of ASCO 2011 abstracts

“…Three articles were derived from the large (n = 411) German primary CNS lymphoma randomized trial of high-dose methotrexate (HD-MTX) with or without ifosfamide followed in patients with a complete response to observation or whole brain RT [14][15][16][17]. The trial demonstrated no advantage to upfront RT and was further analyzed with respect to prognostic variables affecting survival, as well as chemotherapy-related toxicity [18].…”

“…Similarly, chemotherapy-related toxicity was a function of low performance (<70), advanced age (>60 years), receipt of HD-MTX and ifosfamide (compared with HD-MTX only), elevated serum LDH and pre-existing pulmonary or cardiovascular disease [16]. The German primary CNS lymphoma study also analyzed whether evidence of CSF dissemination at diagnosis affected outcome as determined by CSF cytology, polymerase chain reaction (PCR) gene rearrangement or MRI [17]. Despite no intra-CSF chemotherapy being administered in this study, outcome in the 19% of patients with CSF dissemination was similar to that of patients without evidence of CSF dissemination.…”