Originally published as JCO Early Release 10.1200/JCO.2003.04.056 on November 3 2003

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Primary Central Nervous System Lymphoma: Results of a Pilot and Phase II Study of Systemic and Intraventricular Chemotherapy With Deferred Radiotherapy

Hendrik Pels, Ingo G.H. Schmidt-Wolf, Axel Glasmacher, Holger Schulz, Andreas Engert, Volker Diehl, Anton Zellner, Gabriele Schackert, Heinz Reichmann, Frank Kroschinsky, Marlies Vogt-Schaden, Gerlinde Egerer, Udo Bode, Carlo Schaller, Martina Deckert, Rolf Fimmers, Christoph Helmstaedter, Aslihan Atasoy, Thomas Klockgether, Uwe Schlegel

From the Departments of Neurology, Internal Medicine, Pediatric Hemato-Oncology, and Neurosurgery, Institute of Biostatistics, and Department of Epileptology, Neuropsychological Unit, University of Bonn, Bonn; Departments of Internal Medicine and Neuropathology, University of Cologne, Cologne; Departments of Neurosurgery, Neurology, and Internal Medicine, University of Dresden, Dresden; and Departments of Neurology and Internal Medicine, University of Heidelberg, Heidelberg, Germany.

Address reprint requests to U. Schlegel, MD, Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str 25, D-53105 Bonn, Germany; e-mail: uwe.schlegel{at}uni-bonn.de.

Purpose: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy.

Patients and Methods: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)–based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C.

Results: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%).

Conclusion: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.

Presented in part at the Annual Meeting of the American Society of Hematology 2002.

Both H.P. and I.G.H.S.-W. contributed equally to this work.

Related Correspondence

• Is Withdrawal of Consolidation Radiotherapy an Evidence-Based Strategy in Primary Central Nervous System Lymphomas?
  Michele Reni and Andrés J.M. Ferreri
  JCO 2004 22: 1165-1167 [Full Text]

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• In Reply:
  K. Hoang-Xuan and J.Y. Delattre
  JCO 2004 22: 1167-1168 [Full Text]

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