原发中枢神经系统淋巴瘤的治疗

原发中枢神经系统淋巴瘤（PCNSL）是一种少见的非霍奇金淋巴瘤（NHL），其治疗观念在过去的20年中发生了巨大的改变，现总结探索其治疗方式的研究工作。     

原发中枢神经系统淋巴瘤的治疗

原发中枢神经系统淋巴瘤(PCNSL)是一种少见的非霍奇金淋巴瘤(NHL),其治疗观念在过去的20年中发生了巨大的改变,现总结探索其治疗方式的研究工作.     

17例复发性原发中枢神经系统淋巴瘤的临床观察

目的 探讨原发性中枢神经系统淋巴瘤（PCNSL）复发后的临床特征、影像学特点、治疗疗效和预后。方法 回顾性分析2008年6月至2012年6月我科收治的17例复发性PCNSL患者的临床资料。复发后7例PCNSL患者行大剂量（900mg／m²）培美曲塞化疗;10例行替莫唑胺+奈达铂+长春新碱联合化疗,其中3例联合局部照射20～30Gy,3例患者行Ommaya囊置入术,术后给予利妥昔单抗30mg经Ommaya囊内注射治疗。结果 全组患者脑实质内异位复发9例（52.9％）,原位复发5例（29.4％）,脑脊膜转移2例（11.8％）,颅外腰椎转移1例（5.9％）。多体素质子磁共振波谱（1H-MRS）检查显示,全组患者肿瘤实质区及瘤周近侧水肿区胆碱（Cho）峰升高及N 乙酰天门冬氨酸（NAA）、肌酸（Cr）峰降低,肿瘤实质区有明显升高的Lip峰。复发PCNSL患者经治疗后有6例（35.3％）获CR,4例（23.5％）PR,5例（29.4％）SD,2例（11.8％）PD,有效率（RR）为58.8％（10／17）。至随访截止时间,全组患者的中位生存期（OS）为111个月,含替莫唑胺方案与培美曲塞方案患者的中位OS无明显差异（P＞0.05）。结论 PCNSL以脑内异位复发为主,复发后治疗困难,预后差,含替莫唑胺或培美曲塞综合治疗可能有一定程度的获益。     

利妥昔单抗联合适形放疗治疗术后原发中枢神经系统淋巴瘤的疗效分析

 【摘要】　目的 探讨利妥昔单抗结合全颅放射治疗、局部三维适形放疗（3D-CRT）加量治疗术后原发中枢神经系统淋巴瘤（PCNSL）的疗效。方法　PCNSL术后患者23例,年龄均＜60岁,全颅放射治疗处方剂量32.4 Gy,局部病灶采用3D-CRT推加剂量至50.4 Gy,放射治疗第1天开始使用利妥昔单抗（375 mg／m2）,每周1次,连续使用6周。用Kaplan-Meier法分析患者的生存情况。结果　23例患者中,完全缓解19例（82.6 ％）,部分缓解3例（13.0 ％）;无进展生存14例（60.9 ％）,无病生存期26个月（17～34个月）,总生存期为40个月（29～55个月）;无Ⅲ～Ⅳ级神经毒性出现。结论 利妥昔单抗联合全颅放疗、病灶部位3D-CRT推量的方案治疗年龄＜60岁的术后PCNSL患者可以获得较长的生存期,而且治疗的不良反应低。     

利妥昔单抗联合大剂量甲氨蝶呤在原发性中枢神经系统淋巴瘤患者中的应用效果

目的 探讨利妥昔单抗联合大剂量甲氨蝶呤在原发性中枢神经系统淋巴瘤患者中的应用效果.方法 按照入院顺序将84例原发性中枢神经系统淋巴瘤患者分为对照组和观察组,每组42例,对照组接受大量甲氨蝶呤治疗,观察组患者接受利妥昔单抗联合大剂量甲氨蝶呤治疗.比较两组患者的临床疗效、不良反应、生存期和生活质量.结果 观察组患者的治疗总...     

利妥昔单抗联合化疗治疗老年原发性中枢神经系统淋巴瘤疗效分析

摘 要：［目的］ 评价利妥昔单抗联合化疗在老年原发性中枢神经系统淋巴瘤（PCNSL）中的治疗效果。［方法］ 2010年10月至2013年10月收治的PCNSL患者91例,随机分为利妥昔单抗联合化疗组（R-MAD组）(n＝31)给予利妥昔单抗375mg/m2、大剂量甲氨蝶呤3.5g/m2、阿糖胞苷0.5～1.0g/m2及地塞米松10mg/d治疗;靶向治疗组(n＝30)采用大剂量甲氨喋呤3.5g/m2联合利妥昔单抗375mg/m2联合化疗;传统治疗组(n＝31)采用全脑放疗加大剂量甲氨喋呤3.5g/m2治疗。比较各组疗效、不良反应、1年和3年生存率。［结果］ （1）R-MAD组、靶向治疗组及传统治疗组完全缓解率分别为54.84%、33.33%和16.67%（χ2=10.856,P=0.004）;总有效率分别为83.87%、66.67%和53.33%（χ2=6.592,P=0.037）。（2）R-MAD组的血液系统、肝脏毒性、胃肠道反应及神经毒性不良反应的发生率明显低于传统治疗组（P<0.05）,R-MAD组的骨髓抑制发生率明显高于靶向治疗组及传统治疗组（P＜0.05）。（3）R-MAD组1年和3年的生存率高于靶向治疗组和传统治疗组（χ2=7.715、8.139,P=0.021、0.017）。［结论］利妥昔单抗、大剂量甲氨蝶呤、阿糖胞苷及地塞米松联合应用治疗老年PCNSL可提高治疗效果,延长患者的生存时间,但不增加不良反应。     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤的临床分析

目的 观察利妥昔单抗联合CHOP方案治疗CD20阳性B细胞非霍奇金淋巴瘤的临床疗效及毒副反应.方法 8例B细胞非霍奇金淋巴瘤均采用利妥昔单抗联合化疗,利妥昔单抗375 ms/m2于每1周期化疗前1天静脉滴注,每3周为1疗程,4～6周期后评价疗效及毒副反应.结果 8例患者中,CR 7例,PR 1例,总有效率100%.主要...     

原发中枢神经系统淋巴瘤诊疗进展

原发中枢神经系统淋巴瘤是一种少见的中枢神经系统恶性肿瘤,以大剂量甲氨蝶呤为基础方案诱导化疗是目前一线治疗,随后全脑放疗作为巩固治疗.迟发神经认知功能障碍出现,尤其是老年人,使缓解患者是否需要全脑放疗或减量放疗需要进一步明确.利妥昔单抗治疗PCNSL,初步研究表明美罗华可能给患者带来获益,但研究证据水平较低.HDC/ASCT对于治疗复发性或难治性PCNSL虽有疗效但毒副作用较大,临床价值尚存争议.     

原发中枢神经系统淋巴瘤的治疗进展

原发中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）是仅累及脑实质、脊髓、眼、颅神经及脑膜 ,无中枢神经（central nervous system,CNS）以外部位受累的一类结外非霍奇金淋巴瘤。目前,治疗主要是以大剂量甲氨蝶呤为基础的化疗,联合大剂量化疗/自体干细胞移植（autologous stem cell transplantation,auto-HSCT）或减量的全脑放疗。但缓解率较低,不良反应较大。研究显示,10%～15%的患者对诱导化疗原发耐药,即使治疗有效,仍有50%的患者复发。近年来,PCNSL遗传学和分子的研究极大地促进了生物学机制的理解。小分子药物和靶向药物治疗的前景可观,有望减少不良反应的同时,提高患者缓解率、延长寿命。本文主要对目前PCNSL的新治疗方向进行综述。      

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma:a prospective phase Ⅱ trial

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone(R-FPD) regimen followed by whole-brain radiotherapy(WBRT) for patients with primary central nervous system lymphoma(PCNSL).Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen cons...     

Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma

BACKGROUND:

Despite initial treatment with high‐dose methotrexate‐based regimens, many patients with primary central nervous system lymphoma (PCNSL) relapse and die from their disease. No standard of care exists at progression or relapse, but chemotherapy and in some cases radiation are usually used. Pemetrexed is a multitargeted antifolate, similar to methotrexate, but with a broader spectrum of activity. Because methotrexate is an integral part of PCSNL treatment, the authors assessed the antitumor activity and safety of pemetrexed in recurrent PCNSL.

METHODS:

Patients with relapsed/refractory PCNSL were enrolled in this trial. Treatment consisted of pemetrexed 900 mg/m² given every 3 weeks with low‐dose dexamethasone, folate, and B12 supplementation. Each cycle was 6 weeks, and follow‐up imaging was done before each new cycle. Treatment was continued until complete remission, progression, or toxicity.

RESULTS:

Eleven patients were treated, with a median age of 69.8 years and Karnofsky performance status of 70%; 10 of 11 patients had failed prior high‐dose methotrexate. The median number of pemetrexed cycles given was 5, with an associated overall response rate of 55% and disease control rate of 91%. The 6‐month progression‐free survival (PFS) was 45%, median PFS was 5.7 months, and median overall survival was 10.1 months. Toxicities were primarily hematologic and infectious.

CONCLUSIONS:

Pemetrexed has single‐agent activity in relapsed/refractory PCNSL. Toxicities were seen likely because of the higher than standard dose used. Further investigation of this agent or other multitargeted antifolates in PCNSL is warranted to determine optimal dose and efficacy in a more homogeneous population. Cancer 2012. © 2011 American Cancer Society.     

原发中枢神经系统恶性淋巴瘤的诊断及治疗

目的：探讨原发中枢神经系统恶性淋巴瘤（PCNSL）的临床、影像学表现,治疗方案选择和预后。方法：对24例PCNSL的诊断、治疗过程、预后进行回顾性分析。结果：PCNSL的临床表现以颅内压增高、局灶占位性病变损伤症状为主,肿瘤可单发或多发;肿瘤影像学缺乏特异性,确诊依靠病理学诊断。结论：PCNSL恶性度高,预后不良,手术全切率低;对确诊病例采用个体化的手术方案结合术后放、化疗是治疗本病的关键,可显著延长患者生存时间。     

Second malignancies in patients with primary central nervous system lymphoma

Background

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma with distinctive biological behaviors. The evolving treatment of PCNSL has greatly improved the outcome for patients with this disease and has stimulated interest in second malignancies (SMs) in patients diagnosed with PCNSL.

Methods

The records of 129 cases of PCNSL at Mayo Clinic, diagnosed between January 1, 1988, and November 26, 2012, were reviewed. Data on clinical characteristics, laboratory parameters, treatments, outcomes, and SMs were collected. The mean follow-up time was 44.8 months (range, 0.5–240 months; median, 28.0 months).

Results

Altogether, 28 cases with 30 (23.26%) SMs were identified. Twenty (15.50%) patients had prior or synchronous SM. Ten (7.76%) patients developed a subsequent primary cancer after PCNSL. The most common sites of prior or synchronous SMs were prostate (4/20), skin (4/20), and gastrointestinal (3/20). The most common site of the subsequent SM was skin (4/10). Two cases were identified with both prior SM and subsequent SM.

Conclusions

Second malignancies in cases with PCNSL were not uncommon and occurred in nearly a quarter of our cohort. Nonmelanoma skin cancers were frequently seen. Therefore, screening for SMs should also be considered in long-term follow-up of patients with PCNSL. In addition, the high incidence of subsequent cancer, synchronous cancer, and frequently seen nonmelanoma skin cancers may all indicate an immunosuppressed state in patients with PCNSL.     

原发中枢神经系统恶性淋巴瘤的诊断及治疗

目的:探讨原发中枢神经系统恶性淋巴瘤(PCNSL)的临床、影像学表现,治疗方案选择和预后. 方法: 对24例PCNSL的诊断、治疗过程、预后进行回顾性分析. 结果: PCNSL的临床表现以颅内压增高、局灶占位性病变损伤症状为主,肿瘤可单发或多发;肿瘤影像学缺乏特异性,确诊依靠病理学诊断. 结论: PCNSL恶性度高,预后不良,手术全切率低;对确诊病例采用个体化的手术方案结合术后放、化疗是治疗本病的关键,可显著延长患者生存时间.     

Prolonged remission of primary central nervous system lymphoma after discontinuation of steroid therapy

Summary The case of a 63-year old man is presented in whom remission of a primary central nervous system lymphoma was achieved by corticosteroids only. After discontinuation of steroid therapy the remission persisted for two and a half years. Recurrences appeared at other sites of the brain, and were steroid resistant.     

原发性中枢神经系统淋巴瘤患者预后的影响因素分析

目的 探讨原发性中枢神经系统淋巴瘤(PCNSL)患者预后的影响因素.方法 收集82例PCNSL患者的临床资料,包括性别、年龄、病灶数量、病灶部位、病灶直径、治疗方法、意识状态、体力状况(PS)评分等一般资料,以及脑脊液(CSF)常规检测指标(CSF蛋白质、CSF氯化物)和生化检测指标[血清乳酸脱氢酶(LDH)、β2微球...     

Proton magnetic resonance spectroscopy in immunocompetent patients with primary central nervous system lymphoma

Background: Magnetic resonance spectroscopy imaging (MRSI) non-invasively evaluates the metabolic profile of normal and abnormal brain tissue. Primary central nervous system lymphoma (PCNSL) is a highly aggressive tumor responsive to high-dose methotrexate based regimens. Patients often have complete responses but relapses are common. We characterized the MR spectra of PCNSL patients, correlated MRSI with MRI and evaluated whether early recurrence could be detected by MRSI.Methods: Patients with PCNSL had multi-voxel MRSI before, during, and after treatment. The region of interest was defined using axial FLAIR images. Metabolites assessed were N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate. Ratios of Cho/Cr, NAA/Cho, and NAA/Cr were calculated and correlated with MRI. Overall survival (OS), progression free survival (PFS), and relative risks of each of the ratios were determined.Results: MRSI was performed on 11 men and seven women; median age of 59. Sixty-seven MRSI studies were performed, 17 baseline and 48 follow-up studies. Median ratios in 16 pretreated patients were Cho/Cr-1.90, NAA/Cho-0.39, and NAA/Cr-1.27. Two patients had lipid at baseline, five had lactate and two had both. MRSI correlated with tumor response or progression on MRI; in three patients MRSI suggested disease progression prior to changes on MRI. Univariate analysis of metabolite ratios, lipid, and lactate revealed that none significantly affected PFS or OS. Kaplan–Meier analysis of the presence or absence of lipid, lactate or both revealed a trend for increased PFS.Conclusion: MRSI and MRI correlate with tumor response or progression and may allow early detection of disease recurrence. The presence or absence of lipid and/or lactate may have prognostic significance. Further research using MRSI needs to be done to validate our findings and determine the role of MRSI in PCNSL.Presented in part at the 1999 Annual Meeting of the American Academy of Neurology; April 12, 1999.