High Dose-Chemotherapy Followed By Autologous Peripheral Blood Stem Cell Transplantation for Patients with Refractory or Recurrent Primary Central Nervous System Lymphoma –Results of a Multicenter Study By the Germany Collaborative PCNSL Study Group
Authors: Illerhaus Gerald , Fritsch Kristina , Schmidt-Wolf Ingo , Schroers Roland , Egerer Gerlinde , Korfel Agnieszka , Birnbaum Tobias , Lamprecht Monika , von Bubnoff Nikolas , Wolf Hans-Heinrich , Stilgenbauer Stephan , Trepel Martin , Möhle Robert , Hader Claudia , Ihorst Gabriele , Fricker Heidi , Kasenda Benjamin , Schorb Elisabeth , Finke Jürgen 
Published: October 2019

Abstract
Introduction: Primary central nervous system lymphoma (PCNSL) relapses in up to 60% after conventional chemotherapy. The prognosis of refractory or recurrent PCNSL is very poor with a median survival of up to 5 months. Whole brain radiotherapy may improve survival up to 10 months, but is associated with significant neurotoxicity. High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) have demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). To evaluate the efficacy of this approach, we initiated a prospective multicenter phase II study with HDT and ASCT for relapsed PCNSL. This trial is registered at ClinicalTrials.gov (NCT 00647049)
Patients and Methods: Thirty eight pts. <65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 2 cycles of Rituximab (3,75mg/m²), AraC (2x 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization after the 1st cycle. Conditioning regimen included BCNU (400 mg/m2) and TT (4x5 mg/kgBW) followed by ASCT. Patients not in complete remission after HDT and ASCT underwent WBRT.
Results: From 2007 to 2012, 38 pts (18 female, 20 male) with relapsed (n=31) or refractory (n=7) PCNSL from 10 German centers were enrolled and evaluable for analysis (median age 58 years, range 37-66 years). All pts had aggressive B-cell lymphomas (DLBCL). Median Karnofsky performance status at diagnosis was 90% (range 60-100). Patients were intensively pretreated, all pts underwent HD-MTX within the first-line-treatment, 15 of 38 pts were treated within the Bonn protocol. Thirty-one of 38 pts (81,6%) received HDT and ASCT according to protocol. Three pts died before PBSCT, 4 further pts were treated off study due to PD (n=2), refusal of HDT (n=1) and insufficient stem cell harvest (n=1). Regarding the primary endpoint in the intent-to-treat population, 22 pts (57,9%) achieved complete (CR) and and 5 (13,2%) partial remission (PR) after HDT and ASCT, respectively. In patients treated per protocol, the CR and PR-rate rate was 71% and 16,1% respecticely. The overall respinse rate in the per protocol population was 86,1%. Six pts in PR after HDT and ASCT received consolidating WBRT. After a median 39-month follow-up (range 0-48 mo), 1 and 2 years OS was 63% and 57%, respectively. Median survival of the intent-to-treat population was 29 months. Further results will be presented.
Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as salvage therapy for pts. with relapsed or refractory PCNSL.

Disclosures
Illerhaus: Riemser: Honoraria. Wolf:Bayer: Honoraria; Geo Pharma: Honoraria. Stilgenbauer:Pharmacyclics, Janssen: Honoraria, Research Funding.