High-Dose Chemotherapy With Autologous Stem-Cell Transplantation and Hyperfractionated Radiotherapy As First-Line Treatment of Primary CNS Lymphoma

2006 ◽  
Vol 24 (24) ◽  
pp. 3865-3870 ◽  
Author(s):  
Gerald Illerhaus ◽  
Reinhard Marks ◽  
Gabriele Ihorst ◽  
Roland Guttenberger ◽  
Christoph Ostertag ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Clinical Improvement ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Purpose To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. Patients and Methods Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. Results Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). Conclusion Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.

scholarly journals SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Eisei Kondo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hematopoietic Stem

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Primary CNS Lymphoma: Updated Results from a Pilot and Phase II Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3594-3594
Author(s):  
Gerald Illerhaus ◽  
Fabian Müller ◽  
Friedrich Feuerhake ◽  
J.ürgen Finke
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Pilot Trial ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Abstract Introduction: High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). A 5-year overall survival probability (OS) of 69% could be demonstrated in 30 pts within a phase-II trial on HDT and ASCT with consolidating whole-brain-irradiation (WBRT) (Illerhaus et al. JCO 2006). A subsequent pilot trial on HDT and ASCT without WBRT showed a 5-year OS of 77% (Illerhaus et al. Haematologica 2008). Here we give an update of our two different treatment regimens and future perspectives. Patients and Methods: Thirty pts. ≤65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 3 cycles of high-dose methotrexate (MTX, 8 g/m2), 1 cycle of AraC (2× 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization. Conditioning regimen included BCNU (400 mg/m2) and TT (2×5 mg/kgBW) followed by ASCT. Hyperfractionated WBRT (45 Gy, 2×1Gy/d) was administered as consolidation. In our subsequent pilot trial 13 pts. (age 38–67 years) were treated without consolidating WBRT; CHT was intensified with 4 cycles MTX 8g/m2, 2 cycles AraC (2× 3 g/m2) and TT (40 mg/m2). Dose escalated HDT included BCNU (400 mg/m2) and TT (4×5 mg/kgBW) followed by ASCT. WBRT was reserved for pts. not responding to CHT. Results: Median follow-up of the 30 pts. treated within our phase II trial was extended to 95 months (mo), the updated 5-year OS of all pts. is 66.6% and 82,3% of the subgroup of pts. who underwent HDT and ASCT (n=23), respectively. Three additional deaths occurred due to relapse (n=2) after 45 and 71 mo and due to comorbidity (n=1) after 103 mo. Five of 30 pts. developed severe leukoencephalopathy during follow-up. With a median follow-up of 35 mo in the 13 pts. treated within the pilot-phase without consolidating WBRT 3-year OS of all pts. is 77%. No further relapse or non-relapse mortality occurred in this pilot-group during. Most recent follow-up data will be presented in detail. Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as initial therapy for pts. with PCNSL. The restriction of WBRT to refractory disease shows similar OS rates and a decrease in neurotoxicity. In an ongoing multicenter phase-II trial immunotherapy with rituximab is combined with HDT and ASCT to further increase remission rates. A future randomized trial should be focused on the efficacy of consolidation with HDT supported by ASCT.

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study

2019 ◽  
Vol 37 (10) ◽  
pp. 823-833 ◽  
Author(s):  
Caroline Houillier ◽  
Luc Taillandier ◽  
Sylvain Dureau ◽  
Thierry Lamy ◽  
Mouna Laadhari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
Intensive Chemotherapy ◽  
Free Survival

PURPOSE To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

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