Annals of Oncology Advance Access originally published online on December 21, 2006
Annals of Oncology 2007 18(4):665-671; doi:10.1093/annonc/mdl458
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© 2006 European Society for Medical Oncology
hematologic malignancies |
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 Hämato-Onkologie OSHO-53 phase II study
1 Department of Internal Medicine C, Hematology and Oncology, Stem Cell Transplantation, Ernst-Moritz-Arndt-University, Greifswald, Germany
2 Division of Hematology and Oncology, University of Leipzig, Leipzig
3 Department of Internal Medicine IV, Hematology and Oncology, Martin-Luther-University Halle-Wittenberg, Halle/Saale
4 Department of Hematology-Oncology-Bone Marrow Transplantation, Chemnitz Hospital, Chemnitz
5 Department of Internal Medicine, Hematology and Oncology, Hospital Ernst-von-Bergmann, Potsdam
6 Department of Radiotherapy, Ernst-Moritz-Arndt-University, Greifswald
7 Department of Neurology, Ernst-Moritz-Arndt-University, Greifswald
8 Department of Internal Medicine, BFA-Hospital Ückeritz, Ückeritz, Germany
* Correspondence to: Prof. Dr G. Dölken, Ernst-Moritz-Arndt-Universität Greifswald, Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie—Transplantationszentrum, Sauerbruchstraße, 17475 Greifswald. Tel: +49-3834-866698; Fax +49-3834-866713; E-mail: michael.montemurro{at}chuv.ch
Background: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma.
Patients and methods: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT.
Results: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1–69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan–Meier), after HD-BuTT 27 months and ‘not reached’, respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively.
Conclusion: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.
Key words: autologous stem-cell transplantation, CNS lymphoma, high-dose chemotherapy, methotrexate, neurotoxicity, PCNSL
These authors contributed equally to the paper. Received for publication May 13, 2006. Revision received October 18, 2006. Accepted for publication October 25, 2006.
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