High-Dose Chemotherapy and Stem Cell Transplantation for Primary CNS Lymphoma

Author(s):  
Carole Soussain ◽  
Patrick Johnston ◽  
Gerald Illerhaus
2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Eisei Kondo

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.


2006 ◽  
Vol 24 (24) ◽  
pp. 3865-3870 ◽  
Author(s):  
Gerald Illerhaus ◽  
Reinhard Marks ◽  
Gabriele Ihorst ◽  
Roland Guttenberger ◽  
Christoph Ostertag ◽  
...  

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.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3594-3594
Author(s):  
Gerald Illerhaus ◽  
Fabian Müller ◽  
Friedrich Feuerhake ◽  
J.ürgen Finke

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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3342-3342 ◽  
Author(s):  
Michael Montemurro ◽  
Thomas Kiefer ◽  
Frank Schüler ◽  
Haifa-Katrin Al Ali ◽  
Hans-Heinrich Wolf ◽  
...  

Abstract Purpose: This multicenter study investigated the efficacy and safety of high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa with autologous stem-cell transplantation (HD-BuTT) and response-adapted whole-brain radiotherapy (WBRT) in patients with newly diagnosed primary CNS lymphoma. Patients and methods: 23 patients (median age 55 years) were treated in five centres. Patients received HD-MTX (4h-infusion; 8g/m2; >60y: 6g/m2) on d1 and d10 followed by leucapheresis. Then patients were stratified according to their results on neuroimaging: In case of at least a partial response, HD-BuTT consisting of 16mg busulfan / 10mg thiotepa per kg body weight followed by peripheral stem cell transplantation was given. Patients without response to induction or without complete response after high-dose therapy received WBRT (45Gy) as further treatment. Results: 16 patients received the planned treatment with HD-MTX followed by HD-BuTT. CR / PR rates for these patients were 19 % / 69 % after HD-MTX, 69 % / 13 % after HD-BuTT, 81 % / 6 % after HD-BuTT plus WBRT, respectively. Included the patients with early WBRT due to toxicity (n=2) and non-responders to HD-MTX induction (n=4) the overall response rate for all 23 patients was 83 % (intention-to-treat). Outcome was significantly influenced by the response to MTX-induction. There were three treatment-related deaths. Irradiated patients (n=9) had a high incidence of severe neurotoxicity leading to death in 3 patients. At a median follow-up of 15 months the median EFS and OS for all patients were 17 and 20 months, after HD-BuTT 27 months and “not reached”, respectively. Patients older than 60 years and younger patients have achieved similar outcomes. Conclusion: This study showed that HD-methotrexate induction followed by HD-BuTT is a feasible treatment option for newly diagnosed primary CNS lymphoma. Patients achieving CR after HD-BuTT show no signs of clinical neurotoxicity with median survival not reached yet. Time on treatment is 2–3 months only, but the induction treatment needs improvement to be more effective. WBRT in this study was associated with a high incidence of severe neurotoxicity and should therefore be avoided.


2001 ◽  
Vol 28 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Roy D. Baynes ◽  
Roger D. Dansey ◽  
Jared L. Klein ◽  
Caroline Hamm ◽  
Mark Campbell ◽  
...  

2017 ◽  
Vol 63 (2) ◽  
pp. 326-328
Author(s):  
Larisa Filatova ◽  
Yevgeniya Kharchenko ◽  
Sergey Alekseev ◽  
Ilya Zyuzgin ◽  
Anna Artemeva ◽  
...  

Currently there is no single approach to treatment for aggressive diffuse large-cell B-cell lymphoma (Double-HIT and Triple-HIT). Accumulated world data remain controversial and, given the unfavorable prognosis in this subgroup, high-dose chemotherapy with autologous stem cell transplantation in the first line of treatment is a therapeutic option.


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