High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma

T. Cheng, P. Forsyth, A. Chaudhry, D. Morris, S. Glück, J. A. Russell, D. A. Stewart

Research output: Contribution to journalArticle

100 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)679-685
Number of pages7
JournalBone Marrow Transplantation
Volume31
Issue number8
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Fingerprint

Thiotepa
Busulfan
Cyclophosphamide
Lymphoma
Radiotherapy
Stem Cells
Transplants
Brain
Central Nervous System
Drug Therapy
Methotrexate
Recurrence
Therapeutics
Karnofsky Performance Status
Ataxia
Dementia
Disease Progression

Keywords

  • Autologous stem cell transplant
  • Busulfan
  • High-dose chemotherapy
  • Primary CNS lymphoma
  • Thiotepa

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. / Cheng, T.; Forsyth, P.; Chaudhry, A.; Morris, D.; Glück, S.; Russell, J. A.; Stewart, D. A.

In: Bone Marrow Transplantation, Vol. 31, No. 8, 01.04.2003, p. 679-685.

Research output: Contribution to journalArticle

Cheng, T. ; Forsyth, P. ; Chaudhry, A. ; Morris, D. ; Glück, S. ; Russell, J. A. ; Stewart, D. A. / High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. In: Bone Marrow Transplantation. 2003 ; Vol. 31, No. 8. pp. 679-685.
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AB - 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.

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