scholarly journals Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen

2020 ◽  
Vol 20 (7) ◽  
pp. 468-479
Author(s):  
Patricia A. Young ◽  
Daria Gaut ◽  
Davis K. Kimaiyo ◽  
Jonathan Grotts ◽  
Tahmineh Romero ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Survival Outcomes ◽  
High Dose ◽  
Secondary Central Nervous System

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

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2527-2527
Author(s):  
Gerald Illerhaus ◽  
Kristina Fritsch ◽  
Ingo Schmidt-Wolf ◽  
Roland Schroers ◽  
Gerlinde Egerer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Median Survival ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Intent To Treat ◽  
Treat Population

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.

Excellent Outcomes in Patients with Primary and Secondary Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using a Rituximab, Busulfan, Melphalan, Thiotepa Conditioning Regimen

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Shona Philip ◽  
Adrienne Fulford ◽  
Selay Lam ◽  
Chai Wye Phua ◽  
Joy Mangel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Central Nervous System Lymphoma ◽  
Pet Ct ◽  
Secondary Central Nervous System

Introduction: Historically, CNS lymphomas have been associated with a very poor prognosis High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) with promising results in small recent small prospective phase 1/2 results and retrospective series. We hypothesized that the use of R-BuMelTt (rituximab, busulfan, melphalan, thiotepa) conditioning regimen with ASCT regimen will be effective for both patients with PCNSL and SCNSL as used in previously reported promising data by Oh et al 2016 for patients with SCNSL with higher remission and survival rates. Patients and Methods: A retrospective analysis was performed of 6 consecutive patients who had undergone R-BuMelTt conditioning regimen with ASCT for 3 patients with PCNSL and 3 patients with SCNSL from December 2017 to March 2020. The median age of this patient population was 62 years at the time of ASCT. The induction chemotherapy regimen used for patients with SCNSL was R-CHOMP except one patient who received DHAP, and for patients with PCNSL MATRix regimen was used. The median duration of chemotherapy cycles was 4, and all of them had achieved remission prior to transplant based on PET/CT scan/MRI scan. All patients were planned to undergo ASCT using the Conditioning Regimen of Rituximab 375 mg/m2 on Day-7, Thiotepa 250 mg/m2 on Day-6,-5, Busulfan 3.2 mg/kg on Day-4,-3,-2 and Melphalan 100 mg/m2 on Day-1. Supportive cares measures were given at treating physician's discretion. Results: Patients received a median cell dose of 4.4x106 CD34+cells/kg (range: 2.5-5.7), had neutrophil engraftment at 11.5 days (range:9-13), platelet recovery was achieved on days 11,15 and 16 for three patients but was delayed at 27, 46, 89 days for 3 patients. Infectious complications were common with documented bacteremia in in 3 out of 6 patients, 2 patients with c. difficile infection and with significant platelet support due to thrombocytopenia. At a median follow up of 24.5 months (range: 6-30 months), 5 out of 6 patients had complete metabolic response on radiological imaging with PET/CT in conjunction with MRI head. One of the patients with SCNSL died after transplant due to CNS relapse 223 days post ASCT giving an overall survival of 66.6%. Amongst the 2 patients with SCNSL that survived there was no relapse after 30 month follow-up. None of the patients with PCNSL died or relapsed during or after transplant therefore having a 100% overall survival. Although this is a small retrospective study, our results are comparable to current literature. Toxicities included nausea/vomiting, diarrhea, mucositis with 5/6 patients requiring TPN. Also busulfan PK levels were not done. Conclusions: R-BuMelTt regimen can be used successfully as conditioning regimen for ASCT for patients with PCNSL and SCNSL, however with increased hematological toxicity, most notably delayed platelet engraftment. The rate of progression free and overall survival is promising with short median follow up of 24 months. Disclosures Lam: Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau.

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