Abstract
We investigated the feasibility of i.v. BU, CY and etoposide (BUCYE), followed by auto-SCT (ASCT) in patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The planned treatment consisted of induction chemotherapy with five cycles of high-dose MTX and two cycles of high-dose cytarabine followed by conditioning with BUCYE (BU 3.2 mg/m2, day −7 to day −5; CY 50 mg/kg, day −3 to day −2 and etoposide 200 mg/m2, twice a day, days −5 and −4) and then ASCT. Between May 2005 and November 2008, 11 consecutive PCNSL patients were treated. All patients completed the treatment as planned, with no cases of treatment-related death or veno-occlusive disease. After BUCYE and ASCT, 10 patients achieved complete response (CR) or unconfirmed CR (CRu). Two patients, one partial response and one CRu, received further whole-brain radiotherapy, with all achieving CR. At a median follow-up of 25.0 months (8.8–50.7 months), six patients had relapsed, with a median event-free interval of 15.0 months (95% confidence interval, 4.5–25.6 months). Median survival time was not reached yet with a 2-year survival rate of 88.9%. The current treatment was feasible with a favorable tolerance profile. However, further regimen optimization is necessary because of high relapse rate.
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References
Abrey LE, DeAngelis LM, Yahalom J . Long-term survival in primary CNS lymphoma. J Clin Oncol 1998; 16: 859–863.
DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ . Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002; 20: 4643–4648.
Brevet M, Garidi R, Gruson B, Royer B, Vaida I, Damaj G . First-line autologous stem cell transplantation in primary CNS lymphoma. Eur J Haematol 2005; 75: 288–292.
Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A et al. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant 2006; 38: 417–420.
Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P et al. 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. J Clin Oncol 2003; 21: 4151–4156.
Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol 2006; 24: 3865–3870.
Illerhaus G, Muller F, Feuerhake F, Schafer AO, Ostertag C, Finke J . High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica 2008; 93: 147–148.
Montemurro M, Kiefer T, Schuler F, Al-Ali HK, Wolf HH, Herbst R et al. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol 2007; 18: 665–671.
Cheng T, Forsyth P, Chaudhry A, Morris D, Gluck S, Russell JA et al. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant 2003; 31: 679–685.
Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol 2008; 26: 2512–2518.
Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 2001; 19: 742–749.
Kroger N, Hoffknecht M, Hanel M, Kruger W, Zeller W, Stockschlader M et al. Busulfan, cyclophosphamide and etoposide as high-dose conditioning therapy in patients with malignant lymphoma and prior dose-limiting radiation therapy. Bone Marrow Transplant 1998; 21: 1171–1175.
Hanel M, Kroger N, Sonnenberg S, Bornhauser M, Kruger W, Kroschinsky F et al. Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma. Ann Hematol 2002; 81: 96–102.
Aggarwal C, Gupta S, Vaughan WP, Saylors GB, Salzman DE, Katz RO et al. Improved outcomes in intermediate- and high-risk aggressive non-Hodgkin lymphoma after autologous hematopoietic stem cell transplantation substituting intravenous for oral busulfan in a busulfan, cyclophosphamide, and etoposide preparative regimen. Biol Blood Marrow Transplant 2006; 12: 770–777.
Copelan EA, Penza SL, Pohlman B, Avalos BR, Goormastic M, Andresen SW et al. Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 2000; 25: 1243–1248.
Kim JG, Sohn SK, Chae YS, Yang DH, Lee JJ, Kim HJ et al. Multicenter study of intravenous busulfan, cyclophosphamide, and etoposide (i.v. Bu/Cy/E) as conditioning regimen for autologous stem cell transplantation in patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 2007; 40: 919–924.
Postmus PE, Holthuis JJ, Haaxma-Reiche H, Mulder NH, Vencken LM, van Oort WJ et al. Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration. J Clin Oncol 1984; 2: 215–220.
Kohara H, Ueoka H, Tabata M, Shinagawa K, Hayashi K, Harada M . High-dose etoposide treatment for CNS involvement in a patient with primary non-Hodgkin's lymphoma of the breast. Intern Med 1997; 36: 738–741.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. WHO Classification of Tumours Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer. WHO: Geneva, 2008.
Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003; 21: 266–272.
Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 2005; 23: 5034–5043.
Creaven PJ . The clinical pharmacology of VM26 and VP16-213. A brief overview. Cancer Chemother Pharmacol 1982; 7: 133–140.
Ferreri AJ, Crocchiolo R, Assanelli A, Govi S, Reni M . High-dose chemotherapy supported by autologous stem cell transplantation in patients with primary central nervous system lymphoma: facts and opinions. Leuk Lymphoma 2008; 49: 2042–2047.
Morris PG, Abrey LE . Therapeutic challenges in primary CNS lymphoma. Lancet Neurol 2009; 8: 581–592.
Yang SH, Lee KS, Kim IS, Hong JT, Sung JH, Son BC et al. Long-term survival in primary CNS lymphoma treated by high-dose methotrexate monochemotherapy: role of STAT6 activation as prognostic determinant. J Neurooncol 2009; 92: 65–71.
Acknowledgements
We thank the nurses in the oncology wards and house staff members of the Department of Internal Medicine at Asan Medical Center for their dedication and excellent patient care.
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Yoon, D., Lee, D., Choi, D. et al. Feasibility of BU, CY and etoposide (BUCYE), and auto-SCT in patients with newly diagnosed primary CNS lymphoma: a single-center experience. Bone Marrow Transplant 46, 105–109 (2011). https://doi.org/10.1038/bmt.2010.71
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DOI: https://doi.org/10.1038/bmt.2010.71
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