Lymphoma
Bone Marrow Transplantation (2003) 31, 679–685. doi:10.1038/sj.bmt.1703917
High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma
T Cheng1,2, P Forsyth2,3, A Chaudhry1,2, D Morris1,2, S Glück1,2, J A Russell1,2 and D A Stewart1,2
- 1Department of Medicine, Tom Baker Cancer Centre, University of Calgary, Calgary, Alta., Canada
- 2Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alta., Canada
- 3Department of Clinical Neurosciences, Tom Baker Cancer Centre, University of Calgary, Calgary, Alta., Canada
Correspondence: Dr DA Stewart, Tom Baker Cancer Centre, 1331-28th Street NW, Calgary, Alberta, Canada T2N 2N4
Received 24 April 2002; Accepted 21 November 2002.
Abstract
Treatment of primary central nervous system lymphoma (PCNSL) with combined high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. In an attempt to improve upon these dismal results, we treated seven PCNSL patients with HD-MTX-based induction therapy followed by thiotepa, busulfan, cyclophosphamide (TBC), and autologous stem cell transplant (ASCT), without WBRT. Six of these patients had at least one of the following poor prognostic features: Karnofsky performance status (KPS)
50%, age >60 years, or relapsed disease. All but one patient tolerated the treatment well and experienced improvements in neurological function and overall performance status post-transplant. No treatment-induced neurotoxicity (dementia, ataxia, and incontinence) was observed although the follow-up is short. One early treatment-related death occurred in a patient with multiple comorbid medical conditions. The other six patients achieved a complete response (CR) after TBC and ASCT. Five patients are currently alive and relapse-free at 5, 8, 24, 36, and 42 months from diagnosis. One additional patient relapsed and died 33 months after diagnosis. Two of the seven patients received TBC/ASCT as the only treatment after disease progression following their initial chemotherapy and both remain relapse-free at the time of this report, 22 and 31 months post-TBC/ASCT. In conclusion, prolonged CR can be attained after chemotherapy-only treatment of poor prognosis PCNSL. Furthermore, this small series suggests that high-dose chemotherapy for PCNSL should include drugs that penetrate the CNS such as busulfan and thiotepa rather than standard lymphoma regimens such as BEAM.
Keywords:
high-dose chemotherapy, autologous stem cell transplant, primary CNS lymphoma, busulfan, thiotepa

