Division of Hematology/Oncology, University of California San Francisco, Box 1270, 505 Parnassus Avenue, San Francisco, CA 94143, USA.
Clin Cancer Res. 2012 Feb 15;18(4):1146-55. doi: 10.1158/1078-0432.CCR-11-0625. Epub 2012 Jan 6.
We evaluated a novel therapy for primary central nervous system lymphoma (PCNSL) with induction immunochemotherapy with high-dose methotrexate, temozolomide, and rituximab (MT-R) followed by intensive consolidation with infusional etoposide and high-dose cytarabine (EA). In addition, we evaluated the prognostic value of the minimum apparent diffusion coefficient (ADC(min)) derived from diffusion-weighted MRI (DW-MRI) in patients treated with this regimen.
Thirty-one patients (median age, 61 years; median Karnofsky performance score, 60) received induction with methotrexate every 14 days for 8 planned cycles. Rituximab was administered the first 6 cycles and temozolomide administered on odd-numbered cycles. Patients with responsive or stable central nervous system (CNS) disease received EA consolidation. Pretreatment DW-MRI was used to calculate the ADC(min) of contrast-enhancing lesions.
The complete response rate for MT-R induction was 52%. At a median follow-up of 79 months, the 2-year progression-free and overall survival were 45% and 58%, respectively. For patients receiving EA consolidation, the 2-year progression-free and overall survival were 78% and 93%, respectively. EA consolidation was also effective in an additional 3 patients who presented with synchronous CNS and systemic lymphoma. Tumor ADC(min) less than 384 × 10(-6) mm(2)/s was significantly associated with shorter progression-free and overall survival.
MT-R induction was effective and well tolerated. MT-R followed by EA consolidation yielded progression-free and overall survival outcomes comparable to regimens with chemotherapy followed by whole-brain radiotherapy consolidation but without evidence of neurotoxicity. Tumor ADC(min) derived from DW-MRI provided better prognostic information for PCNSL patients treated with the MTR-EA regimen than established clinical risk scores.
我们评估了一种新的治疗原发性中枢神经系统淋巴瘤（PCNSL）的方法，该方法采用高剂量甲氨蝶呤、替莫唑胺和利妥昔单抗（MT-R）诱导化疗，然后进行密集强化治疗，使用依托泊苷和高剂量阿糖胞苷（EA）。此外，我们评估了这种方案治疗的患者中来自弥散加权 MRI（DW-MRI）的最小表观弥散系数（ADC(min)）的预后价值。
31 名患者（中位年龄 61 岁；中位卡氏功能状态评分 60）接受每 14 天一次的甲氨蝶呤诱导治疗，共 8 个计划周期。第 1 至 6 个周期给予利妥昔单抗，第 1 个周期给予替莫唑胺。对有反应或稳定的中枢神经系统（CNS）疾病的患者给予 EA 巩固治疗。在治疗前的 DW-MRI 中，计算增强病变的 ADC(min)。
MT-R 诱导的完全缓解率为 52%。中位随访 79 个月后，2 年无进展生存率和总生存率分别为 45%和 58%。对于接受 EA 巩固治疗的患者，2 年无进展生存率和总生存率分别为 78%和 93%。另外 3 例同时患有中枢神经系统和全身淋巴瘤的患者也接受了 EA 巩固治疗，同样有效。肿瘤 ADC(min)小于 384×10(-6)mm(2)/s 与较短的无进展生存率和总生存率显著相关。
MT-R 诱导是有效且耐受性良好的。MT-R 联合 EA 巩固治疗的无进展生存率和总生存率与化疗联合全脑放疗巩固治疗相当，但没有神经毒性的证据。DW-MRI 得到的肿瘤 ADC(min)为接受 MTR-EA 方案治疗的 PCNSL 患者提供了比现有临床风险评分更好的预后信息。
