High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission

Cancer. 2017 Aug 15;123(16):3073-3079. doi: 10.1002/cncr.30695. Epub 2017 Apr 3.


Background: High-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) is a therapeutic option for patients with primary central nervous system lymphoma (PCNSL). To the authors' knowledge, data are limited regarding its use among patients in first complete remission (CR1) with the CNS-directed conditioning regimen of thiotepa, busulfan, and cyclophosphamide (TBC).

Methods: A retrospective analysis of patients with PCNSL in CR1 who underwent transplantation using a TBC-based conditioning regimen at 2 academic institutions was performed.

Results: Forty-six consecutive patients who underwent HDC-ASCT while in CR1 were identified. The most common induction regimen was high-dose methotrexate plus temozolomide and rituximab (59%). No patients received whole-brain radiotherapy. A total of 40 patients (87%) received cytarabine before undergoing ASCT as either induction intensification, early consolidation therapy, or mobilization. The median time from diagnosis to transplantation was 6 months (range, 4-15 months). The median age of the patients at the time of transplantation was 59 years (range, 27-69 years). With a median follow-up of 2.7 years after ASCT (range, 6 months-7.5 years), the Kaplan-Meier estimates of 2-year overall survival and progression-free survival were 95% (95% confidence interval [95% CI], 80%-99%) and 92% (95% CI, 77%-97%), respectively. The most common toxicities were severe mucositis (35%) and bacterial infections occurring within 100 days of transplantation (35%). The estimated 2-year nonrecurrence mortality rate was 2.9% (95% CI, 0.2%-13.4%).

Conclusions: HDC-ASCT with a CNS-directed conditioning regimen such as TBC should be considered for patients with PCNSL who are in CR1 because this approach is associated with encouraging disease control and survival in this select patient population. Cancer 2017;123:3073-79. © 2017 American Cancer Society.

Keywords: autologous stem cell transplantation (ASCT); busulfan; cyclophosphamide; high-dose chemotherapy; primary central nervous system lymphoma (PCNSL); thiotepa.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bacterial Infections / etiology
  • Busulfan / administration & dosage
  • Central Nervous System Neoplasms / therapy*
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma / therapy*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Mucositis / etiology
  • Remission Induction
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Temozolomide
  • Thiotepa / administration & dosage
  • Transplantation Conditioning
  • Transplantation, Autologous


  • Cytarabine
  • Rituximab
  • Dacarbazine
  • Cyclophosphamide
  • Thiotepa
  • Busulfan
  • Temozolomide
  • Methotrexate