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.     

Diagnosis and treatment of central nervous system involvement in non-Hodgkin's lymphoma

The diagnosis of lymphoma of the central nervous system (CNS) has been facilitated by advances in neuroimaging and laboratory analysis of cerebrospinal fluid. The most common form of central nervous system CNS involvement in non-Hodgkin's lymphoma (NHL) is leptomeningeal disease. After a diagnosis is established, the use of intrathecal or systemic chemotherapy and radiotherapy can improve survival and palliate symptoms. High-dose systemic chemotherapy with hematopoietic stem cell transplantation is an important treatment option at central nervous system relapse of NHL and for primary CNS lymphoma. The prognosis for disease-free survival and cure is better for patients who have treatment of CNS disease before transplantation than for patients who have active central nervous system disease at the time of transplant.     

Therapie von ZNS-Lymphomen

Primary central nervous system lymphoma (PCNSL) differs from nodal lymphoma with similar histological findings, usually diffuse large B-cell lymphoma, by its strong affinity for the central nervous system (CNS), aggressive course and unusual sensitivity to high-dose methotrexate (HDMTX). Thus, primary therapy of PCNSL is currently based on HDMTX but the optimal chemotherapy regimen has not yet been defined due to the rarity of this disease. In younger patients a cure should be the goal and thus intensified chemotherapy protocols should be considered. Whole brain irradiation does not prolong overall survival when used in primary therapy and thus should not be used routinely. Similar to PCNSL the infrequent CNS involvement of a systemic lymphoma, also called secondary CNS lymphoma, has a very poor prognosis. The scarce data suggest a role for HDMTX-based systemic chemotherapy and high-dose chemotherapy followed by stem cell transplantation for outcome improvement. Avoidance of late neurotoxicity is an important goal in the treatment of PCNSL.     

Magnetic resonance features of primary central nervous system lymphoma in the immunocompetent patient: a pictorial essay

Primary central nervous system lymphoma (PCNSL) is an uncommon but important variant of non-Hodgkin lymphoma and represents up to 6% of all primary central nervous system (CNS) malignancies. Recognition of this entity by radiologist on MRI may avoid unnecessary neurosurgical resection and redirect to biopsy. The pretreatment MRI of patients with biopsy proven PCNSL from the last 5 years at our institution was reviewed. Selected examples were used to construct a pictorial essay to illustrate some of the typical and atypical MR features of PCNSL. MRI of other CNS conditions with imaging similarities to PCNSL was included to demonstrate possible mimics. The typical features of PCNSL lymphoma are intra-axial homogenous single or multiple contrast enhancing lesions, with marked surrounding oedema and restricted diffusion, usually contacting a cerebrospinal fluid (CSF) surface. Necrosis, peripheral enhancement, haemorrhage or calcification are unusual and other diagnoses should be considered if any of these features are present. Potential mimics include high grade glioma, infarcts, metastatic disease, demyelination, abscess and secondary lymphoma. Careful assessment of the MR features and correlation with the clinical findings should enable the radiologists to raise the possibility of PCNSL and minimise the risk of unnecessary resection.     

Advances in the Therapy of Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma (NHL) confined to the nervous system. The management of PCNSL is quite different from the usual treatment of either primary brain tumors or systemic NHL. First-generation chemotherapy regimens used successfully in systemic NHL are ineffective in PCNSL, in large part due to the existence of the blood-brain barrier. Whole-brain radiation therapy (WBRT) results in high response rates but rapid relapse, and this treatment is associated with delayed neurotoxicity in patients with PCNSL. The addition of methotrexate-based chemotherapy has improved survival and lessened toxicity for this patient population. Fundamental issues that remain unresolved in PCNSL include identification of the optimal chemotherapy regimen for newly diagnosed and relapsed PCNSL, the role of WBRT and intrathecal chemotherapy in the treatment of PCNSL, and the optimal management of intraocular lymphoma. Finally, the optimal clinical study design for this rare disease has yet to be defined and implemented.     

Case report of a patient with primary central nervous system lymphoma treated with radioimmunotherapy

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma arising within and confined to the central nervous system and, unlike other primary brain tumors, is very responsive to treatment. Aggressive management can lead to prolonged remissions or cures. However, the prognosis at relapse is generally poor with limited therapeutic options; clearly, new strategies are needed for these patients. Radioimmunotherapy has a growing role in the management of systemic non-Hodgkin lymphoma but has not been evaluated in PCNSL. We report here the first patient with PCNSL treated with radioimmunotherapy.     

Primary central nervous system lymphoma with systemic metastasis: Case report and review

Summary Primary central nervous system lymphoma (PCNSL) almost always remains confined to the nervous system. We report a patient with well documented PCNSL who responded to treatment, but subsequently developed pathologically confirmed systemic metastases without repeated local failure 35 months after initial diagnosis. In a review of the world's literature we identified 5 other cases of PCNSL with histologically confirmed antemortem systemic metastases and a total of 62 cases of central nervous system (CNS) lymphoma in some way associated with extraneural lymphoma. These cases are classified and discussed. Clinicians caring for PCNSL patients must remain alert to the possibility of systemic metastasis, especially as local control of PCNSL improves.     

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.     

Study of radiolabeled indium-111 and yttrium-90 ibritumomab tiuxetan in primary central nervous system lymphoma

BACKGROUND: Therapeutic options for refractory or recurrent primary central nervous system lymphoma (PCNSL) are limited. The blood-brain barrier makes many agents used in systemic lymphomas ineffective in CNS lymphomas. The objective of this study was to determine whether intravenous radioimmunotherapy using anti-CD20 antibody can be delivered to PCNSL. METHODS: This was a single-institution prospective study. Indium-111 ibritumomab tiuxetan was used for imaging and dosimetry. Yttrium-90 ibritumomab tiuxetan at doses of 0.3 to 0.4 mCi/kg were subsequently given for the treatment of recurrent or refractory PCNSL. 111In data were used to estimate radiation doses to lesions delivered by 90Y ibritumomab tiuxetan therapy. RESULTS: Six patients (4 men, 2 women) with a median age of 60 years and median Karnofsky performance status of 70 received both indium-111 and yttrium-90 ibritumomab tiuxetan. The median absorbed dose delivered to the CNS lymphoma was 701 cGy compared with 70 cGy to normal brain. The median progression-free and overall survival times were 6.8 weeks and 14.3 weeks, respectively. CONCLUSIONS: The results from this study suggest that it may be feasible to deliver radiolabeled monoclonal anti-CD20 antibodies as a component of therapy for PCNSL.     

Long-term Survival Following Extra-neural Metastasis From a Pineoblastoma

Primary central nervous system lymphoma (PCNSL) is a rare disease with a poor prognosis. It usually remains confined to central nervous system (CNS). Reports of metastases outside of the CNS are rare. We report a patient with well-documented PCNSL who responded to treatment, but subsequently developed a histologically confirmed subcutaneous metastasis to the left leg without local failure.     

Management of primary intraocular lymphoma

Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which malignant lymphoid cells invade the retina, vitreous body, or optic nerve head. It is usually a large B-cell non-Hodgkin’s lymphoma. PIOL typically presents as a vitritis that is unresponsive to corticosteroid therapy. Diagnosis of PIOL requires pathologic confirmation of malignant cells in specimens of the cerebrospinal fluid, vitreous, or chorioretinal biopsies. The optimal therapy for PIOL has yet to be determined. It is generally believed that PIOL should be treated with a combination of systemic chemotherapy, including high-dose methotrexate and radiotherapy. However, several new developments for PIOL with central nervous system involvement have been reported, including intrathecal therapy and autologous stem-cell transplantation. In addition, intravitreal methotrexate has been successful in the treatment of isolated recurrent ocular disease. This article provides an overview of treatment modalities for initial, recurrent, and relapsed PIOL.     

Primary T-cell CNS lymphoma presenting with leptomeningeal spread and neurolymphomatosis

Primary CNS lymphoma (PCNSL), a rare form of non-Hodgkin lymphoma that is confined to the brain, is usually of B-cell origin. Primary leptomeningeal lymphoma, regardless of T or B-cell origin, is an unusual site of presentation. Out of 100 consecutive PCNSL patients that we have followed up in our center during the last 10 years, five had T-cell lymphoma (5%). All presented with leptomeningeal involvement as the sole manifestation and four of them presented with neuronal lymphomatosis. Presenting symptoms included signs of elevated intracranial pressure with 6th nerve palsy; headache and bilateral 3rd nerve palsy; mononeuritis multiplex and unilateral hearing loss; bilateral 7th nerve paralysis and bilateral uveitis. Because neither the CSF nor the MRI were indicative, meningeal or nerve biopsies were required for conclusive diagnosis. Four patients died 10-19 months from disease onset and one patient is alive 36 months following the diagnosis. We conclude that T-cell PCNSL can present as an isolated leptomeningeal involvement which may be associated with neurolymphomatosis affecting cranial and peripheral nerves. These manifestations mimic other neurological conditions such as pseudotumor cerebri or vasculitis. Diagnosis is difficult and, as a result, frequently delayed. This calls for early consideration of meningeal or nerve biopsy whenever CSF findings are inconclusive.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

Clinical aspects and management of AIDS-related lymphoma

The incidence of non-Hodgkin's lymphoma (NHL) is increased by approximately 100-fold in patients with advanced HIV infection. Clinical presentations may include systemic lymphoma, primary central nervous system (CNS) lymphoma, and primary effusion lymphoma. Systemic lymphoma is the most common presentation, is almost always of intermediate or high-grade histology and B-cell phenotype, and usually involves extranodal sites. The disease is potentially curable with combination chemotherapy used for immunocompetent patients with lymphoma, although cure is achieved in only approximately 10–35% of patients. Primary CNS lymphoma may be difficult to distinguish from cerebral infection. The prognosis is very poor, although approximately 10% of patients selected for therapy may survive beyond 1 year with brain irradiation. Attention to infection prophylaxis and antiretroviral therapy is important. Evidence suggests that highly active antiretroviral therapy (HAART) has resulted in a decreased incidence of lymphoma, and that patients with systemic lymphoma treated in the post-HAART era have a better prognosis.     

Primary central nervous system lymphoma: essential points in diagnosis and management

Primary central nervous system lymphoma (PCNSL) is an extra-nodal non-Hodgkin lymphoma. PCNSL is defined as lymphoma involving the brain, leptomeninges, eyes, or spinal cord without evidence of lymphoma outside the CNS. Treatment includes induction with chemotherapy and consolidation with whole-brain radiotherapy or high-dose chemotherapy supported by autologous stem cell transplantation. High-dose methotrexate is the most important drug in cases with PCNSL, and this drug will be used in combination with small molecules, BTK inhibitors, new monoclonal antibodies, and checkpoint blockers.     

Primäre Zentralnervensystemlymphome (PZNSL)

Primary central nervous system lymphoma (PCNSL) comprises about 2?% of intracranial tumors. The vast majority of these tumors are diffuse large B-cell lymphomas; however, PCNSL differs from nodal lymphoma with a similar histopathology by its strong affinity for the CNS with infrequent systemic involvement, by its usually aggressive course and unusually high sensitivity to high-dose methotrexate (HDMTX). Thus, HDMTX represents the backbone of current therapy although the optimal treatment protocol for PCNSL has not yet been established due to the paucity of occurrence. Age and general condition of the patient are the most important prognostic factors. In younger patients curing is the goal and can probably be achieved in a fraction of patients by application of intensified chemotherapy protocols. In the elderly, however, a cure is mostly not possible and therapy optimization is still urgently needed. To spare patients with PCNSL the potentially devastating consequences of delayed treatment-related CNS toxicity is an important goal.     

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。     

Chemotherapy in newly diagnosed primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment.     

A case with coincidental diagnosis of primary central nervous system lymphoma and lymph node sarcoidosis

Primary central nervous system lymphoma (PCNSL) is rare. Clinical and histological differential diagnosis of systemic lymphoma and sarcoidosis continues to be a challenge. The first case report in the German and English literature of PCNSL and synchronous sarcoidosis is presented. Synchronous mediastinal lymphadenopathy suggestive of non-Hodgkin’s lymphoma (NHL) or sarcoidosis was noted. Both conditions require alternative therapeutic and prognostic considerations to PCNSL. A regime of intrathecal and adjuvant systemic chemotherapy led to transient clinical improvement prior to the patient’s demise through overwhelming sepsis and multiorgan failure. Post mortem findings confirmed synchronous PCNSL with mediastinal lymph node sarcoidosis.