High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial

被引：131

作者：

Illerhaus, Gerald ^{[1
,23
]}

Kasenda, Benjamin ^{[1
,3
]}

Ihorst, Gabriele ^{[2
]}

Egerer, Gerlinde ^{[4
]}

Lamprecht, Monika ^{[5
]}

Keller, Ulrich ^{[6
]}

Wolf, Hans-Heinrich ^{[7
]}

Hirt, Carsten ^{[8
]}

Stilgenbauer, Stephan ^{[9
]}

Binder, Mascha ^{[10
,11
]}

Hau, Peter ^{[12
,13
]}

Edinger, Matthias ^{[14
]}

Frickhofen, Norbert ^{[15
]}

Bentz, Martin ^{[16
]}

Moehle, Robert ^{[17
]}

Roeth, Alexander ^{[18
]}

Pfreundschuh, Michael ^{[19
]}

von Baumgarten, Louisa ^{[20
]}

Deckert, Martina ^{[21
]}

Hader, Claudia ^{[22
]}

Fricker, Heidi ^{[23
]}

Valk, Elke ^{[1
]}

Schorb, Elisabeth ^{[23
]}

Fritsch, Kristina ^{[23
]}

Finke, Juergen ^{[23
]}

机构：

[1] Klinikum Stuttgart, Dept Haematol Oncol & Palliat Care, D-70174 Stuttgart, Germany

[2] Univ Freiburg, Med Ctr, Clin Trials Unit, Freiburg, Germany

[3] Royal Marsden Hosp, Dept Med, London, England

[4] Heidelberg Univ, Dept Haematol & Oncol, Heidelberg, Germany

[5] Univ Hosp Schleswig Holstein, Dept Internal Med 2, Kiel, Germany

[6] Tech Univ Munich, Dept Med 2, Munich, Germany

[7] Univ Hosp Halle, Dept Haematol & Oncol, Halle, Germany

[8] Ernst Moritz Arndt Univ Greifswald, Hematol & Oncol Clin Internal Med, Greifswald, Germany

[9] Univ Ulm, Dept Internal Med 3, Ulm, Germany

[10] Univ Med Ctr Hamburg Eppendorf, Dept Internal Med 2, Oncol Hematol, Hamburg, Germany

[11] Univ Med Ctr Hamburg Eppendorf, Bone Marrow Transplantat Sect Pneumol, Hamburg, Germany

[12] Univ Hosp Regensburg, Dept Neurol, Regensburg, Germany

[13] Univ Hosp Regensburg, Wilhelm Sander NeuroOncol Unit, Regensburg, Germany

[14] Univ Hosp Regensburg, Dept Med, Regensburg, Germany

[15] HELIOS Dr Horst Schmidt Kliniken, Dept Haematol & Oncol, Wiesbaden, Germany

[16] Stadt Klinikum Karlsruhe, Med Klin, Karlsruhe, Germany

[17] Univ Tubingen, Dept Haematol & Oncol, Tubingen, Germany

[18] Univ Duisburg Essen, Fac Med, Dept Haematol, Essen, Germany

[19] Univ Saarland, Klin Innere Med 1, Homburg, Germany

[20] Univ Munich, Dept Neurol, Munich, Germany

[21] Univ Hosp Cologne, Inst Neuropathol, Cologne, Germany

[22] Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany

[23] Albert Ludwigs Univ, Univ Med Hosp, Dept Hematol Oncol & Stem Cell Transplantat, Freiburg, Germany

来源：

Lancet Haematology | 2016年 / 3卷 / 08期

关键词：

CENTRAL-NERVOUS-SYSTEM; WHOLE-BRAIN RADIOTHERAPY; NON-HODGKIN-LYMPHOMA; 1ST-LINE TREATMENT; CENTER EXPERIENCE; RADIATION-THERAPY; RESPONSE CRITERIA; CLINICAL-TRIALS; PLUS RITUXIMAB; FOLLOW-UP;

D O I：

10.1016/S2352-3026(16)30050-3

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma. Methods In this prospective, single-arm, phase 2 trial, we recruited patients aged 18-65 years with newly diagnosed primary CNS lymphoma and immunocompetence, with no limitation on clinical performance status, from 15 hospitals in Germany. Patients received five courses of intravenous rituximab 375 mg/m(2) (7 days before first high-dose methotrexate course and then every 10 days) and four courses of intravenous high-dose methotrexate 8000 mg/m(2) (every 10 days) and then two courses of intravenous rituximab 375 mg/m(2) (day 1), cytarabine 3 g/m(2) (days 2 and 3), and thiotepa 40 mg/m(2) (day 3). 3 weeks after the last course, patients commenced intravenous HCT-ASCT (rituximab 375 mg/m(2) [day 1], carmustine 400 mg/m(2) [day 2], thiotepa 2 x 5 mg/kg [days 3 and 4], and infusion of stem cells [day 7]), irrespective of response status after induction. We restricted radiotherapy to patients without complete response after HCT-ASCT. The primary endpoint was complete response at day 30 after HCT-ASCT in all registered eligible patients who received at least 1 day of study treatment. This trial is registered at ClinicalTrials. gov, number NCT00647049. Findings Between Jan 18, 2007, and May 23, 2011, we recruited 81 patients, of whom two (2%) were excluded, therefore we included 79 (98%) patients in the analysis. All patients started induction treatment; 73 (92%) commenced HCT-ASCT. 61 (77.2% [95% CI 66.1-86.6]) patients achieved a complete response. During induction treatment, the most common grade 3 toxicity was anaemia (37 [47%]) and the most common grade 4 toxicity was thrombocytopenia (50 [63%]). During HCT-ASCT, the most common grade 3 toxicity was fever (50 [68%] of 73) and the most common grade 4 toxicity was leucopenia (68 [93%] of 73). We recorded four (5%) treatment-related deaths (three [4%] during induction and one [1%] 4 weeks after HCT-ASCT). Interpretation HCT-ASCT with thiotepa and carmustine is an effective treatment option in young patients with newly diagnosed primary CNS lymphoma, but further comparative studies are needed.

引用

页码：E388 / E397

页数：10

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