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Upfront autologous stem-cell transplantation with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED) in patients with newly diagnosed primary central nervous system lymphoma

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Abstract

Treatment of primary central nervous system lymphoma (PCNSL) improved in recent years. However, the high neurotoxicity and low survival rates associated with this condition remain unresolved. We report 13 consecutive patients with PCNSL for whom upfront melphalan, cyclophosphamide, etoposide, and dexamethasone (known as LEED) followed by autologous stem-cell transplantation (ASCT) was planned at the Anjo Kosei Hospital. All patients were pathologically diagnosed with diffuse large B-cell lymphoma and were negative for human immunodeficiency virus. All patients were to receive three cycles of high-dose methotrexate-based induction chemotherapy, two cycles of high-dose AraC-based chemotherapy, and LEED followed by ASCT. All 13 patients achieved a partial response, and the 3-year overall survival (OS) rate was 76.2 %. Seven of the 13 patients were alive at the last follow-up, without any adverse events, including neurotoxicity. Six of the 13 (46.2 %) patients underwent ASCT and the 3-year OS rate was 80.0 %. Although this study included only a limited number of patients, these preliminary signs of efficacy and tolerability merit further consideration. To make further improvements in survival, the rate of patients undergoing ASCT should be increased. Other prospective studies involving greater numbers of patients are required to confirm these findings.

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References

  1. Hochberg FH, Baehring JM, Hochberg EP. Primary CNS lymphoma. Nat Clin Pract Neurol. 2007;3(1):24–35.

    Article  CAS  PubMed  Google Scholar 

  2. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010;11:1036–47.

    Article  CAS  PubMed  Google Scholar 

  3. 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(6):417–20.

    Article  CAS  PubMed  Google Scholar 

  4. Ogura M, Kagami Y, Taji H, Suzuki R, Miura K, Takeuchi T, et al. Pilot Phase 1/2 Study of new salvage therapy (CHASE) for refractory or relapsed malignant lymphoma. Int J Hematol. 2003;77(5):503–11.

    Article  CAS  PubMed  Google Scholar 

  5. Han LN, Zhou J, Hirose T, Imai Y, Ishiguro T, Chou T. Feasibility and efficacy of high-dose melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED) chemotherapy with or without rituximab followed by autologous stem cell transplantation for aggressive and relapsed non-Hodgkin’s lymphoma. Int J Hematol. 2006;84(2):174–81.

    Article  CAS  PubMed  Google Scholar 

  6. Tateishi U. PET/CT in malignant lymphoma: basic information, clinical application, and proposal. Int J Hematol. 2013;98(4):398–405.

    Article  PubMed  Google Scholar 

  7. 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(22):5034–43.

    Article  PubMed  Google Scholar 

  8. 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(2):266–72.

    Article  PubMed  Google Scholar 

  9. Nelson DF, Martz KL, Bonner H. Non-Hodgkin’s lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG):RTOG8315. Int J Radiat Oncol Biol Phys. 1992;23:9.

    Article  CAS  PubMed  Google Scholar 

  10. Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013;31(25):3061–8.

    Article  CAS  PubMed  Google Scholar 

  11. Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007;25(30):4730–5.

    Article  CAS  PubMed  Google Scholar 

  12. Cote GM, Hochberg EP, Muzikansky A, Hochberg FH, Drappatz J, McAfee SL, et al. Autologous stem cell transplantation with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning in patients with CNS involvement by non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2012;18:76–83.

    Article  CAS  PubMed  Google Scholar 

  13. Cheng T, Forsyth P, Chaudhry A, Morris D, Glück 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;31:679–85.

    Article  CAS  PubMed  Google Scholar 

  14. Alimohamed N, Daly A, Owen C, Duggan P, Stewart DA. Upfront thiotepa, busulfan, cyclophosphamide, and autologous stem cell transplantation for primary CNS lymphoma: a single centre experience et al. Leuk Lymphoma. 2012;53(5):862–7.

    Article  CAS  PubMed  Google Scholar 

  15. Yoon DH, Lee DH, Choi DR, Sohn BS, Kim S, Kim SW, 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. 2011;46(1):105–9.

    Article  CAS  PubMed  Google Scholar 

  16. Montemurro M, Kiefer T, Schüler 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;18:665–71.

    Article  CAS  PubMed  Google Scholar 

  17. Kiefer T, Hirt C, Späth C, Schüler F, Al-Ali HK, Wolf HH, et al. Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study. Ann Oncol. 2012;23:1809–12.

    Article  CAS  PubMed  Google Scholar 

  18. Herrlinger U, Küker W, Uhl M, Blaicher HP, Karnath HO, Kanz L, Neuro-Oncology Working Group of the German Society, et al. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol. 2005;57(6):843–7.

    Article  CAS  PubMed  Google Scholar 

  19. Guha-Thakurta N, Damek D, Pollack C, Hochberg FH. Combination and the effect of adding high-dose AraC to MTX in patients with newly diagnosed primary CNS lymphoma. J Neurooncol. 1999;43(3):259–68.

    Article  CAS  PubMed  Google Scholar 

  20. Hiraga S, Arita N, Ohnishi T, Kohmura E, Yamamoto K, Oku Y, et al. Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas. J Neurosurg. 1999;91(2):221–30.

    Article  CAS  PubMed  Google Scholar 

  21. Slevin ML, Piall EM, Aherne GW, Harvey VJ, Johnston A, Lister TA. Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid. J Clin Oncol. 1983;1(9):546–51.

    CAS  PubMed  Google Scholar 

  22. Gouyette Alain, Hartmann Olivier, Pico Jose-Luis. Pharmacokinetics of high-dose melphalan in children and adults. Cancer Chemother Pharmacol. 1986;16:184–9.

    Article  CAS  PubMed  Google Scholar 

  23. 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(10):738–41.

    Article  CAS  PubMed  Google Scholar 

  24. Fortin D, McAllister LD, Nesbit G, Doolittle ND, Miner M, Hanson EJ, et al. Unusual cervical spinal cord toxicity associated with intra-arterial carboplatin, intra-arterial or intravenous etoposide phosphate, and intravenous cyclophosphamide in conjunction with osmotic blood brain-barrier disruption in the vertebral artery. Am J Neuroradiol. 1999;20:1794–802.

    CAS  PubMed  Google Scholar 

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Correspondence to Kotaro Miyao.

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Miyao, K., Sakemura, R., Imai, K. et al. Upfront autologous stem-cell transplantation with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED) in patients with newly diagnosed primary central nervous system lymphoma. Int J Hematol 100, 152–158 (2014). https://doi.org/10.1007/s12185-014-1608-9

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  • DOI: https://doi.org/10.1007/s12185-014-1608-9

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