Early relapses in patients with primary CNS lymphoma treated with methotrexate-based chemotherapy without consolidating
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CLINICAL STUDY
Early relapses in patients with primary CNS lymphoma treated with methotrexate-based chemotherapy without consolidating whole brain irradiation Tobias Birnbaum • Katja Bochmann • Louisa von Baumgarten • Andreas Straube
Received: 31 August 2012 / Accepted: 6 January 2013 / Published online: 17 January 2013 Ó Springer Science+Business Media New York 2013
Abstract Methotrexate (MTX)-based chemotherapy is used as upfront treatment for most patients with primary CNS lymphoma. Whether consolidating whole brain irradiation (WBI) should be recommended for patients who achieve complete remission (CR) is still a matter of debate. Patients who are predicted to experience an early relapse (ER, B12 months from diagnosis) might especially benefit from consolidating treatment. We therefore evaluated the incidence and prognostic impact of ER in patients with CR following chemotherapy without WBI. We identified 40 patients between 2000 and 2010 who had achieved CR following MTX-based chemotherapy. Of 36 evaluable patients 11 (31 %) experienced an ER. These patients had significantly impaired overall survival (46.0 vs. 79.0 months, p = 0.001). Normal cerebrospinal fluid cell count (11.0 vs. 76.0 months, p = 0.001) and frequent reduction of MTX dose due to impaired creatinine clearance (10.0 vs. 48.0 months, p = 0.005) had a significantly negative impact on relapse-free survival. Patients with CR following MTXbased induction chemotherapy represent a heterogeneous population. In these patients, ER is an independent risk factor for impaired overall survival. Therefore, these patients might especially benefit from consolidating treatment. These results have to be validated by prospective trials.
T. Birnbaum (&) L. von Baumgarten A. Straube Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany e-mail: [email protected] [email protected] K. Bochmann Department of Neuroradiology, Ludwig-MaximiliansUniversity, Marchioninistr. 15, 81377 Munich, Germany
Keywords PCNSL Early relapse Prognosis CSF Methotrexate
Introduction There is no standard of care defined for patients with primary central nervous system lymphoma (PCNSL). Most experts recommend high-dose methotrexate (MTX)-based chemotherapy as an upfront strategy. With this approach complete remission (CR) is achieved in the majority of patients [1–6]. There is broad consensus that patients without CR following induction chemotherapy should be treated with salvage whole brain irradiation (WBI) or with high-dose chemotherapy followed by autologous stem-cell transplantation (HDC-ASCT) within clinical trials. In contrast, it is still a matter of debate if consolidation treatment should be recommended in patients who achieve CR after MTX-based chemotherapy as well. Small phase-2 trials suggest that HDC-ASCT could lead to higher cure rates when used as first-line treatment, but data from randomized trials proving the superiority of this strategy are still lacking [7–9]. Furthermore, HDC-ASCT is feas
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