Journal of Clinical Oncology, Vol 21, Issue 22
(November), 2003: 4151-4156
© 2003 American Society for Clinical Oncology
Intensive Methotrexate and Cytarabine Followed by High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Patients With Newly Diagnosed Primary CNS Lymphoma: An Intent-to-Treat Analysis
Lauren E. Abrey,
Craig H. Moskowitz,
Warren P. Mason,
Michael Crump,
Douglas Stewart,
Peter Forsyth,
Nina Paleologos,
Denise D. Correa,
Nicole D. Anderson,
Dawn Caron,
Andrew Zelenetz,
Stephen D. Nimer,
Lisa M. DeAngelis
From the Departments of Neurology and Medicine and the Office of Clinical Research, Memorial Sloan-Kettering Cancer Center, New York, NY; Princess Margaret Hospital, University of Toronto, Toronto; Tom Baker Cancer Center, University of Calgary, Calgary, Canada; and the Department of Neurology, Evanston Hospital, Northwestern University, Chicago, IL.
Address reprint requests to Lauren Abrey, MD, Memorial Sloan-Kettering Cancer Center, Department of Neurology, 1275 York Ave, New York, NY 10021; e-mail: abreyl{at}mskcc.org.
Purpose: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL).
Patients and Methods: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue.
Results: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity.
Conclusion: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.
Presented in part at the 37th American Society of Clinical Oncology Annual Meeting, San Francisco, CA, May 12–15, 2001.
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