ASH 2016 | High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for Relapsed or Refractory Primary CNS Lymphoma – a Prospective Multicenter Trial by the German Cooperative PCNSL Study Group

The 58th Annual Meeting & Exposition of the American Society of Hematology’s (ASH) took place in San Diego, CA, and on December 5th, Benjamin Kasenda, MD, PhD, from the Haematology/Oncology Center at Klinikum-Stuttgart, Germany, presented data from a prospective single-arm, multi-center, phase-II trial conducted by the German Cooperative PCNSL Study Group.

  • Treatment: 2 courses rituximab, thiotepa, high-dose cytarabine followed by HCT-ASCT regardless of response. No CR following HCT-ASCT underwent whole-brain radiotherapy (WBRT)
  • 39 pts from 12 centers, <66 years old (median=57yr) who failed prior HD-MTX therapy. Of these, 28 were relapsed, 8 refractory
  • 4% responded to induction before HCT-ASCT (4CR, 18PR)
  • 1% pts underwent HCT-ASCT (32pts), after this CR=56.4% (22pts), PR=15.4% (6pts)

  • Overall 2 year OS = 56.4% and PFS = 46%
  • Following HCT-ASCT 1yr PFS = 62.5%. 2yr PFS = 56.1%

  • In the ITT population, 1yr PFS = 51.3%. 2yr PFS = 46.0%
  • 1yr and 2yr OS in the ITT population are 61.5% and 56.4%


In conclusion it was stated that short-induction therapy, like that outlined here, followed by HCT-ASCT is effective in R/R PCNSL patients having failed prior HD-MTC therapy, but comparative studies will need to be published to further analyze the role of HCT-ASCT.


  1. Kasenda B. et al. High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for Relapsed or Refractory Primary CNS Lymphoma – a Prospective Multicentre Trial By the German Cooperative PCNSL Study Group. 2016 December 5; Oral Abstract #781: ASH 58th Annual Meeting and Exposition, San Diego, CA.



Purpose: To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in patients with relapsed or refractory primary CNS lymphoma (PCNSL).

Patients and methods: We conducted a single-arm multicentre phase 2 study for immunocompetent patients (<66 years of age) with PCNSL failing prior HD-MTX based chemotherapy. Induction treatment consisted of 2 courses of rituximab (rituximab 375mg/m2), high-dose cytarabine (2 x 3g/m2) and thiotepa (40mg/m2) with collection of autologous stem cells in between. Conditioning treatment for HCT-ASCT consisted of rituximab 375mg/m2, carmustine 400mg/m2 and thiotepa (4 x 5mg/kg). Patients commenced HCT-ASCT irrespective of response status after induction. Only patients not achieving complete remission (CR) after HCT-ASCT received whole brain radiotherapy (WBRT). The primary endpoint was CR after HCT-ASCT by intention-to-treat (ITT). Secondary endpoints included safety, progression free survival (PFS, time to progression or death) and overall survival (OS, time to death due to any cause).

Results: Between May 2007 and July 2012, we enrolled 39 patients from 12 German centres. The median age and Karnofsky performance score was 57 years (range 37 to 65) and 90% (range 60% to 100%), respectively. 28 (71.8%) patients had relapsed and 8 (28.2%) refractory disease. 22 (56.4%) patients responded to induction (4 CR, 18 partial remissions [PR]) and 32 (82.1%) patients commenced HCT-ASCT. 22 patients (56.4%, 95% CI 39.6% to 72.2%) achieved CR after HCT-ASCT, 6 (15.4%) achieved PR, and 1 (2.6%) had stable disease. In 9 (17.8%) patients the final scan was not done, because 7 (18.0%) did not undergo HCT-ASCT and 2 died (5.1%) during HCT-ASCT procedure. After a median follow-up of 45.2 months, the respective 2-year PFS and OS rates were 46.0% (95% CI 30.3% to 61.7%, median PFS 12.4 months, Figure 1) and 56.4% (95% CI 40.8% to 72.0%); median OS not reached (Figure 2). The non-relapse mortality rate was 10.3% (95% CI 4.1% to 26.0%) at 1 year without any further increase afterwards. In the subset of 32 patients who received HCT-ASCT, 14 (56.3%) experienced progression or died translating into 1 and 2-year PFS rates (calculated from date of HCT-ASCT) of 62.5% (95% CI 45.7% to 79.3%) and 56.1% (95% CI 38.8% to 73.3%) with no further decrease afterwards. Main grade 3 or higher toxicities were hematological as expected. We recorded four (10.3%) treatment-related deaths, 2 during induction and 2 during HCT-ASCT.

Conclusions: In eligible PCNSL patients failing HD-MTX based chemotherapy, a short induction with high-dose cytarabine and thiotepa followed by HCT-ASCT is an effective treatment option. Our data provide a reliable benchmark for future comparative studies needed to further scrutinize the role of HCT-ASCT in the salvage setting for PCNSL. 


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