Three Cases Treated with High-dose Cytarabine and Etoposide followed by Autologous Stem Cell Transplantation for Relapsed Primary CNS Lymphoma

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.

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The influence of rituximab, high-dose therapy followed by autologous stem cell transplantation, and age in patients with primary CNS lymphoma

Annals of Hematology ◽

10.1007/s00277-015-2470-4 ◽

2015 ◽

Vol 94 (11) ◽

pp. 1853-1857 ◽

Cited By ~ 16

Author(s):

M. Madle ◽

I. Krämer ◽

N. Lehners ◽

M. Schwarzbich ◽

P. Wuchter ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Therapy ◽

Dose Therapy

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

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.005 ◽

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.

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Primary CNS Lymphoma—Radiation-Free Salvage Therapy by Second Autologous Stem Cell Transplantation

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2010.11.011 ◽

2011 ◽

Vol 17 (2) ◽

pp. 281-283 ◽

Cited By ~ 12

Author(s):

Benjamin Kasenda ◽

Elisabeth Schorb ◽

Kristina Fritsch ◽

Claudia Hader ◽

Jürgen Finke ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Salvage Therapy ◽

Primary Cns Lymphoma ◽

Cns Lymphoma

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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

Journal of Clinical Oncology ◽

10.1200/jco.18.00306 ◽

2019 ◽

Vol 37 (10) ◽

pp. 823-833 ◽

Cited By ~ 27

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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Nivolumab maintenance after salvage autologous stem cell transplantation results in long-term remission in multiple relapsed primary CNS lymphoma

European Journal Of Haematology ◽

10.1111/ejh.13072 ◽

2018 ◽

Vol 101 (1) ◽

pp. 115-118 ◽

Cited By ~ 7

Author(s):

Denis Terziev ◽

Barbara Hutter ◽

Barbara Klink ◽

Albrecht Stenzinger ◽

Fabian Stögbauer ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Primary Cns Lymphoma ◽

Cns Lymphoma

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

Lymphoma and Leukemia of the Nervous System ◽

10.1007/978-1-4419-7668-0_9 ◽

2010 ◽

pp. 155-168

Author(s):

Carole Soussain ◽

Patrick Johnston ◽

Gerald Illerhaus

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Primary Cns Lymphoma ◽

High Dose Chemotherapy ◽

Cns Lymphoma ◽

High Dose

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Primary CNS Lymphoma Treated with HD-Methotrexate, HD-Busulfan/Thiotepa, Autologous Stem Cell Transplantation and Response-Adapted Whole-Brain Radiotherapy: Results of the Multicenter OSHO-53 Phase II - Study.

Blood ◽

10.1182/blood.v106.11.3342.3342 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3342-3342 ◽

Cited By ~ 2

Author(s):

Michael Montemurro ◽

Thomas Kiefer ◽

Frank Schüler ◽

Haifa-Katrin Al Ali ◽

Hans-Heinrich Wolf ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Primary Cns Lymphoma ◽

Whole Brain Radiotherapy ◽

Cns Lymphoma ◽

High Dose ◽

Newly Diagnosed ◽

Brain Radiotherapy ◽

High Incidence

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.

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