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

American Society of Clinical Oncology (ASCO) - Tập 21 Số 22 - Trang 4151-4156 - 2003
Lauren E. Abrey1, Craig H. Moskowitz1, Warren Mason1, Michael Crump1, Douglas A. Stewart1, Peter Forsyth1, Nina A. Paleologos1, Denise D. Correa1, Nicole D. Anderson1, D Caron1, Andrew D. Zelenetz1, Stephen D. Nimer1, Lisa M. DeAngelis1
1From 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.

Tóm tắt

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.

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Tài liệu tham khảo

Deangelis LM: Current management of primary central nervous system lymphoma. Oncology 9:63,1995–76,

10.1056/NEJM199304083281404

10.1200/JCO.2000.18.17.3144

10.1200/JCO.2002.11.013

10.3171/jns.1994.81.2.0188

10.1200/JCO.1998.16.3.859

10.1212/WNL.48.Suppl_5.18S

10.1056/NEJM199512073332305

10.1200/JCO.2001.19.3.742

10.1007/s11912-001-0061-0

10.1200/JCO.2000.18.16.3025

10.1002/(SICI)1097-0142(20000201)88:3<637::AID-CNCR22>3.0.CO;2-Y

Edelstein M, Vietti T, Valeriote F: The enhanced cytotoxicity of combinations of 1-beta-D-arabinofuranosylcytosine and methotrexate. Cancer Res 35:1555,1975–1558,

10.1172/JCI109525

10.1080/01621459.1958.10501452

10.1200/JCO.2003.01.117

Santini G, Coser P, Congiu AM, et al: VACOP-B, high-dose cyclophosphamide and high-dose therapy with peripheral blood progenitor cell rescue for aggressive non-Hodgkin’s lymphoma with bone marrow involvement: A study by the non-Hodgkin’s Lymphoma Co-operative Study Group. Haematologica 85:160,2000–166,

10.1200/JCO.2003.03.036

10.1200/JCO.2002.20.24.4615

10.1093/jnci/93.1.4

10.1002/ana.10102

10.1016/1040-8428(92)90092-5

10.1038/sj.bmt.1703917

Cairncross JG, Swinnen L, Bayer R, et al: Myeloablative chemotherapy for recurrent aggressive oligodendroglioma. J Neurooncol 2:114,2000–119,