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大剂量甲氨蝶呤、长春新碱和洛莫司汀化疗的早期反应-原发性中枢神经系统淋巴瘤的适应性策略:早期完全缓解的患者无需巩固治疗。

Early response to high-dose methotrexate, vincristine, and procarbazine chemotherapy-adapted strategy for primary CNS lymphoma: no consolidation therapy for patients achieving early complete response.

机构信息

Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

出版信息

Ann Hematol. 2014 Feb;93(2):211-9. doi: 10.1007/s00277-013-1853-7. Epub 2013 Aug 1.

Abstract

Optimal treatment strategies for primary central nervous system lymphoma (PCNSL) have not been established. In this study, we investigated the treatment outcomes and prognostic factors of high-dose methotrexate, vincristine, and procarbazine (MVP) chemotherapy followed by an interim response-adapted intensification strategy in immunocompetent patients with PCNSL. We evaluated the evidence of infection with Epstein-Barr virus (EBV) in both brain tumor tissue and whole blood. Forty patients were retrospectively reviewed. Ten (25 %) patients who achieved complete response (CR) in the interim analysis did not receive any additional consolidation treatment after completion of planned high-dose MVP chemotherapy. Additional radiotherapy (n = 9) or autologous stem cell transplantation (ASCT) (n = 7) was performed in patients who did not achieve CR in the interim analysis. The median age was 55 years. The overall CR rate was 62.5 % (n = 25), and the objective response rate was 75.0 %. Two-year overall survival (OS) was 59.8 %, and 2-year progression-free survival was 47.1 %. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 47.5 and 32.5 % of patients, respectively. Treatment-related mortality was 15.0 % (n = 6), and four patients developed delayed neurotoxicity. There was no evidence of EBV-encoded RNA expression in brain tumor tissue. Ten (29.4 %) of 34 patients showed detectable EBV-DNA in whole blood. Poor performance status and EBV-DNA positivity in whole blood were significantly associated with inferior OS (p = 0.032, p = 0.023, respectively). We suggest that high-dose MVP chemotherapy followed by an early response-adapted intensification strategy may be effective and minimize the number of patients who receive radiotherapy or ASCT in the early course of treatment.

摘要

原发性中枢神经系统淋巴瘤 (PCNSL) 的最佳治疗策略尚未确定。在这项研究中,我们研究了在免疫功能正常的 PCNSL 患者中,高剂量甲氨蝶呤、长春新碱和丙卡巴肼 (MVP) 化疗后进行中期反应适应性强化策略的治疗结果和预后因素。我们评估了脑肿瘤组织和全血中 Epstein-Barr 病毒 (EBV) 感染的证据。对 40 例患者进行了回顾性分析。在中期分析中达到完全缓解 (CR) 的 10 例患者(25%)在完成计划的高剂量 MVP 化疗后未接受任何额外的巩固治疗。在中期分析中未达到 CR 的患者接受了额外的放疗 (n=9) 或自体干细胞移植 (ASCT) (n=7)。中位年龄为 55 岁。总缓解率为 62.5%(n=25),客观缓解率为 75.0%。两年总生存率为 59.8%,两年无进展生存率为 47.1%。分别有 47.5%和 32.5%的患者出现 3 级或 4 级中性粒细胞减少症和血小板减少症。治疗相关死亡率为 15.0%(n=6),4 例患者发生迟发性神经毒性。脑肿瘤组织中未检测到 EBV 编码的 RNA 表达。34 例患者中有 10 例(29.4%)全血中可检测到 EBV-DNA。较差的表现状态和全血 EBV-DNA 阳性与较差的 OS 显著相关(p=0.032,p=0.023)。我们建议,高剂量 MVP 化疗后进行早期反应适应性强化策略可能是有效的,并尽量减少治疗早期接受放疗或 ASCT 的患者数量。

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