AIDS-related primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) can develop in the setting of profound immunosuppression, including late-stage infection with HIV. The management of such patients has yet to be defined optimally and differs substantially from that of immunocompetent patients who have PCNSL. The clinical features, diagnosis, and management of AIDS-related PCNSL are reviewed. The authors focus on commonly encountered diagnostic and therapeutic dilemmas and explore some promises and pitfalls of Epstein-Barr virus-directed therapies.     

原发中枢神经系统淋巴瘤研究进展

原发中枢神经系统淋巴瘤(PCNSL)是原发于颅内的结外非霍奇金淋巴瘤,是一种罕见的高侵袭性淋巴瘤,预后较差.近年来,关于PCNSL的治疗方案尚无定论,以往的治疗包括手术、放疗、化疗等.目前大多认为综合治疗可以提高患者的生存率,而联合化疗药物的选择和预防性鞘内注射化疗药物在其治疗中占有重要地位.     

Treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm that has captured popular attention because of its rising incidence and marked chemosensitivity. It is a non-Hodgkins B-cell lymphoma (NHL) that appears confined to the central nervous system (CNS) at presentation but may be multifocal within the brain or involve the leptomeninges or eyes at diagnosis. Like systemic lymphoma, it is highly sensitive to corticosteroids, and administration of steroids should be withheld until the diagnosis has been confirmed histologically. Currently, the initial treatment of choice incorporates high-dose methotrexate (HD-MTX) either as a single agent or in combination with other systemic chemotherapies. Whole-brain radiotherapy (WBRT) can be a highly effective treatment modality when combined with MTX, but the combination causes an unacceptably high incidence of severe permanent neurotoxicity, particularly in patients over age 60. Therefore, chemotherapy alone is the initial treatment of choice in older patients. This approach is also being explored in younger patients, but it is possible that deferring radiotherapy may compromise disease control. Consequently, the role of radiotherapy remains to be clarified in newly diagnosed younger patients with PCNSL.     

Treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) describes a malignant non-Hodgkin's lymphoma (NHL) whose sole site of involvement is the central nervous system (CNS). The diagnosis of PCNSL must be differentiated from systemic NHL with metastasis to the CNS, which usually occurs late in the course of systemic disease. PCNSL accounts for approximately 4% to 7% of primary brain tumors, and its incidence has been increasing since the mid-1970s. Compared with other more common malignant primary brain tumors, PCNSL tends to be more amenable to radiotherapeutic and chemotherapeutic intervention. In this article, the authors review the standard treatment for upfront and recurrent PCNSL.     

原发性中枢神经系统淋巴瘤的治疗

原发性中枢神经系统淋巴瘤(PCNSL)是一种较少见的中枢神经系统恶性肿瘤,总体预后欠佳,主要治疗方法包括手术、放疗和化疗.立体定向活检术以其微创、便捷的优点,已经成为确诊PCNSL的常规方法.全脑放疗是多病灶性PCNSL的标准化治疗方法,可短期内延缓肿瘤进展.以大剂量甲氨蝶呤为基础的治疗方案大大改善了PCNSL的治疗效果,成为PCNSL的有效治疗措施.有效的综合治疗是延长PCNSL患者生存期和改善生命质量的关键.     

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.     

Mutational analysis of primary central nervous system lymphoma

Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.     

Unusual variants of primary central nervous system lymphoma

Rare variants of primary central nervous system lymphoma (PCNSL) include unusual sites of presentation (eg, neurolymphomatosis and primary leptomeningeal lymphoma) and uncommon pathologic entities. Neurolymphomatosis involves peripheral nerves and nerve roots in addition to systemic and central nervous system (CNS) sites. Diagnosis requires a high index of suspicion, and treatment incorporates the principles of therapy for systemic and CNS lymphoma. Primary leptomeningeal lymphoma can present with symptoms of raised intracranial pressure or cranial or spinal polyradiculopathies. Diagnosis can be made by examining cerebrospinal fluid and incorporating immunophenotyping and molecular pathology techniques. Treatment options include irradiation and intrathecal or systemic chemotherapy. The features of PCNSL of T-cell origin and indolent B-cell PCNSL also are discussed.     

An update on primary central nervous system lymphoma

The most important recent advance in treatment of primary central nervous system lymphoma has been the introduction of high-dose methotrexate-based chemotherapy. Convincing data demonstrate that the regimens of such chemotherapy improve survival compared with historical controls treated with radiotherapy alone. However, the optical treatment approach is still unclear and therapy can be associated with long-term neurotoxicity. Current research focuses on maximizing survival while minimizing neurologic sequelae.     

Diagnostic delay in primary central nervous system lymphoma

This study investigates delay in diagnosing primary central nervous system lymphoma (PCNSL), which has a variable clinical and radiological presentation. Early diagnosis and treatment may improve survival and cause less sequela in PCNSL. Medical records of all new cases of PCNSL morphologically verified while alive or by autopsy in Norway in 1989-1998 were reviewed (n = 74). The time from initial symptom to final morphological diagnosis of PCNSL had a median (mean, range) of 70 (106, 22-330) days in 16 AIDS patients and 75 (157, 8-1285) days in 58 non-AIDS patients. Among non-AIDS patients, the time to diagnosis was longer in patients with no tumour in the first neuroimaging report after initial symptom (p = 0.001). Median (mean, range) time from initial symptom to neuroimaging was 14 (25, 1-60) days in AIDS patients and 21 (88, 1-1095) days in non-AIDS patients. In the non-AIDS group, those presenting with personality change or visual disturbance had more delayed imaging than the others. The time from first neuroimaging examination to final diagnosis in non-AIDS patients had a median (mean, range) of 28 (69, 1-845) days, and was longer when no tumour was indicated in the imaging report (p = 0.005) and if first biopsy did not confirm the diagnosis (p = 0.02). All AIDS patients had their diagnosis of PCNSL first established by autopsy. The time from first neuroimaging to autopsy had a median (mean, range) of 48 (81, 10-270) days. There is a considerable delay in the diagnosis of PCNSL and strategies for earlier diagnosis are thus needed. Physicians should consider early neuroimaging in patients with personality changes or visual disturbance, early renewed imaging in patients with persistent neurological symptoms but no tumour on initial imaging, and early/repeated biopsy of focal brain lesions in both AIDS patients and non-AIDS patients.     

Second-line treatment for primary central nervous system lymphoma

Failure after first-line treatment was reported in 35-60% of immunocompetent patients with primary central nervous system lymphoma (PCNSL). There are currently no reports focusing on salvage therapy. This review analyses prognostic factors and the efficacy of salvage therapy by focusing on data from papers reporting results of first-line treatment in 355 cases. The study group consisted of 173 patients presenting treatment failure. The interval between failure and death (TTD) was compared for age at relapse (< or =60 vs. >60 years), type of failure (relapse vs. progression), time to relapse (< or =12 vs. >12 months) and salvage treatment (yes vs no). Median TTD was similar in younger and older patients (P = 0.09). Relapsed patients had a longer TTD than patients with progressive disease (P = 0.002). Early relapse led to a shorter TTD than late relapse (P = 0.005). Median TTD was 14 months for patients who underwent salvage therapy and 2 months for untreated cases (P<0.00001). A multivariate analysis showed an independent prognostic role for salvage therapy and time to relapse. Age and type of failure had no predictive value. Salvage therapy significantly improves outcome and, possibly, quality of life. As many different treatments were used conclusions cannot be made regarding an optimal treatment schedule.     

原发性中枢神经系统淋巴瘤的治疗进展

原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma ,PCNSL ）是一种罕见的结外淋巴瘤,其病理类型多为弥漫性大B 细胞淋巴瘤,影像学多表现为单发的脑实质深部病变,MRI 可有多种强化形态。目前,以大剂量甲氨蝶呤为主的化疗已成为PCNSL 的一线治疗。放、化疗的结合可延长患者的生存期,但神经毒性发生率较高。大剂量化疗联合自体干细胞移植对复发/ 难治性PCNSL 有效。替莫唑胺和利妥昔单抗不良反应小、耐受性好,可作为PCNSL 治疗的选择。PCNSL 的预后受血清LDH浓度、年龄、ECOG 评分/KPS 评分、脑脊液蛋白浓度、肿瘤定位等多种因素的影响。     

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。      

原发性中枢神经系统淋巴瘤治疗进展

原发性中枢神经系统淋巴瘤(PCNSL)的发病率近年来上升明显,如何提高其治疗效果备受关注.随着放疗策略和化疗策略的改变以及新化疗药物的应用,PCNSL的治疗取得了新的进展.     

原发性中枢神经系统淋巴瘤的诊断研究进展

 原发性中枢神经系统淋巴瘤（PCNSL）是一种临床上较为罕见的结外淋巴瘤,病理学分类多为弥漫性大B细胞淋巴瘤。WHO（2008）造血与淋巴组织肿瘤分类将"PCNSL"作为独立疾病实体列出。文章就近年PCNSL的临床诊断研究进展作一介绍。     

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。     

Diagnosis and treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is an uncommon form of non-Hodgkin’s lymphoma (NHL) that has been increasing in incidence over the past three decades. Unlike systemic extranodal NHL, the response to therapy for PCNSL patients has been somewhat unsatisfactory. However, methotrexate-based chemotherapy and whole-brain radiotherapy have improved the outcome of patients. Unfortunately, treatment-related neurotoxicity is common, especially in the elderly. Although progress has been made in treating PCNSL, there remains no optimal methotrexate dose or frequency. Treatment of recurrence also remains controversial. These important questions have prompted several clinical studies looking at novel ways to intensify chemotherapy and limit neurotoxicity.     

Decreasing incidence rates of primary central nervous system lymphoma

BACKGROUND: Incidence rates of primary central nervous system lymphomas (PCNSL) in the U.S. were reported to have increased dramatically during the 1980s and early 1990s. Recent reports portray a continuation of this trend. With potential etiologic factors related to immunosuppression changing, the authors hypothesized that the incidence of PCNSL would be stabilizing. METHODS: The authors analyzed age specific, gender specific, and race specific PCNSL incidence rates from 1973-1998 using data from the Surveillance, Epidemiology, and End Results (SEER) program. To estimate the impact of the acquired immunodeficiency syndrome (AIDS) and organ transplantation on PCNSL trends, the authors evaluated incidence data from the Centers for Disease Control and Prevention HIV [human immunodeficiency virus]/AIDS Surveillance Report, and the United Network for Organ Sharing.RESULTSPCNSL incidence rates decreased from a peak of 10.2 per 1 million person-years in 1995 to 5.1 per 1 million person-years in 1998, a decrease that was largely attributable to a decrease in the incidence of the disease in males age or= 60 years essentially has remained unchanged since 1994, at approximately 16 per 1 million person-years. Since the early 1980s, regardless of age, PCNSL incidence rates were higher in males than in females, and higher in blacks than in whites. Concordant with PCNSL trends, AIDS rates have decreased since their peak in 1993. However, the rate of solid organ transplantations has increased steadily since 1990. CONCLUSIONS: In contrast to recent reports of a progressively increasing incidence, the authors found that PCNSL rates have been decreasing in the majority of demographic groups in the U.S since the mid-1990s. A notable exception was observed in the highest PCNSL risk group, those age >or= 60 years.     

原发性中枢神经系统淋巴瘤的诊断和治疗

原发性中枢神经系统淋巴瘤(PCNSL)是一种较罕见的中枢神经系统恶性肿瘤,其生物学行为具有侵袭性,临床无典型性,病理形态存在异质性,影像表现多样性,依靠病理免疫组织化学及分子生物学方可确诊.各种以大剂量甲氨蝶呤为基础的治疗方案,改善了PCNSL的治疗效果,并成为PCNSL的标准治疗措施,患者的生存率较单用放疗得以显著地提高.早期诊断并进行有效的综合治疗是延长PCNSL患者生存期和改善生活质量的关键.