Abstract
BackgroundTo evaluate outcome and toxicity of High-dose methotrexate (HDMTX)-based induction therapy followed by consolidation with conventional systemic chemotherapy and facultative intraventricular therapy (modified Bonn protocol) in patients with primary CNS lymphoma (PCNSL).MethodsBetween 01/2005 and 12/2013 113 patients with newly diagnosed PCNSL presented at our center; 98 of those qualified for HDMTX based chemotherapy, received a modified Bonn protocol and were included in the analysis. The treatment regimen was based on the “Bonn protocol”, but modified by omission of systemic drugs not able to cross the intact blood brain barrier. Intraventricular therapy was postponed until completion of three induction chemotherapy cycles or was replaced by intrathecal liposomal AraC and rituximab was added to induction from 2010 onwards.ResultsMedian patient age was 67 years (range 38–83). Complete response/complete response unconfirmed (CR/CRu) was achieved in 59/98 patients (60%), partial response (PR) in 9/98 patients (9%). Twenty-four patients (23%) had progressive disease (PD), 6 (6%) died on therapy. Median progression-free survival (PFS) for all patients was 11.4 months, median overall survival (OS) 29.1 months. A trend to better outcome for intraventricular therapy versus intrathecal liposomal AraC was found in patients < 65 years (HR 0.53 [0.19–1.47] for OS and 0.46 [0.21–1.02] for PFS. Ommaya reservoir infection occurred in 3/33 patients (9%).ConclusionsThe data of this single center experience suggest that the outcome with a modified Bonn protocol was comparable to that of the previous regimen, showed fewer Ommaya reservoir infections and may have a trend for better outcome with intraventricular therapy.
Highlights
To evaluate outcome and toxicity of High-dose methotrexate (HDMTX)-based induction therapy followed by consolidation with conventional systemic chemotherapy and facultative intraventricular therapy in patients with primary CNS lymphoma (PCNSL)
Patients and methods All HIV-negative patients, 18 years and older, presenting at this tertiary care center with newly diagnosed and histologically confirmed PCNSL are offered a modified Bonn protocol if they are able to tolerate HDMTX defined by lack of severe organ dysfunction, in particular renal insufficiency with a glomerular filtration rate below 50 ml/min
Of 61 patients treated thereafter, 26 patients were < 65 years. 25/26 patients in group B received intraventricular chemotherapy via an Ommaya reservoir during consolidation. 35 patients treated from 2009 to 2013 were ≥ 65 years, 8 of these patients were treated with intraventricular therapy starting with cycle 4 and 27 patients received no intrathecal therapy at all
Summary
To evaluate outcome and toxicity of High-dose methotrexate (HDMTX)-based induction therapy followed by consolidation with conventional systemic chemotherapy and facultative intraventricular therapy (modified Bonn protocol) in patients with primary CNS lymphoma (PCNSL). In the 1990ies, the combination of HDMTX based chemotherapy with WBRT given for consolidation became treatment of choice in PCNSL, but was associated with a high rate of delayed neurotoxicity, in the elderly [4]. Systemic HDMTX- and High-dose cytarabine (HDAraC)based chemotherapy was applied sequentially and combined in each of six treatment cycles with intraventricular therapy (MTX, prednisolone, AraC) via an Ommaya reservoir. Median overall survival (OS) was 50 months and failure free survival (FFS) 21 month [6] without neurotoxicity at long-term follow-up [8] This protocol has not found broad acceptance due to a 19% rate of Ommaya reservoir infections. A phase II-trial of our group was prematurely stopped, when young patients treated with systemic therapy alone according to the Bonn protocol suffered from early and leptomeningeal relapses [9]
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