Abstract

Purpose:

This multicenter study investigated the efficacy and safety of high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa with autologous stem-cell transplantation (HD-BuTT) and response-adapted whole-brain radiotherapy (WBRT) in patients with newly diagnosed primary CNS lymphoma.

Patients and methods:

23 patients (median age 55 years) were treated in five centres. Patients received HD-MTX (4h-infusion; 8g/m2; >60y: 6g/m2) on d1 and d10 followed by leucapheresis. Then patients were stratified according to their results on neuroimaging: In case of at least a partial response, HD-BuTT consisting of 16mg busulfan / 10mg thiotepa per kg body weight followed by peripheral stem cell transplantation was given. Patients without response to induction or without complete response after high-dose therapy received WBRT (45Gy) as further treatment.

Results:

16 patients received the planned treatment with HD-MTX followed by HD-BuTT. CR / PR rates for these patients were 19 % / 69 % after HD-MTX, 69 % / 13 % after HD-BuTT, 81 % / 6 % after HD-BuTT plus WBRT, respectively. Included the patients with early WBRT due to toxicity (n=2) and non-responders to HD-MTX induction (n=4) the overall response rate for all 23 patients was 83 % (intention-to-treat). Outcome was significantly influenced by the response to MTX-induction. There were three treatment-related deaths. Irradiated patients (n=9) had a high incidence of severe neurotoxicity leading to death in 3 patients. At a median follow-up of 15 months the median EFS and OS for all patients were 17 and 20 months, after HD-BuTT 27 months and “not reached”, respectively. Patients older than 60 years and younger patients have achieved similar outcomes.

Conclusion:

This study showed that HD-methotrexate induction followed by HD-BuTT is a feasible treatment option for newly diagnosed primary CNS lymphoma. Patients achieving CR after HD-BuTT show no signs of clinical neurotoxicity with median survival not reached yet. Time on treatment is 2–3 months only, but the induction treatment needs improvement to be more effective. WBRT in this study was associated with a high incidence of severe neurotoxicity and should therefore be avoided.

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