Secondary central nervous system involvement by non-Hodgkin's lymphoma: the risk factors

The risk of secondary central nervous system (CNS) was estimated in 833 cases of non-Hodgkin's lymphoma diagnosed between January 1975 and December 1988. Fifty-one of them had CNS disease (51/833, 6.1 per cent). No case of low grade lymphoma developed CNS disease. However, 6.5 per cent and 16.7 per cent of patients with intermediate and high grade lymphomas, respectively, had secondary CNS involvement. Stage IV disease and the presence of B symptoms were also associated with an increased risk of CNS disease. Significantly higher incidence of CNS disease was seen in patients with lymphoma involving orbit (43 per cent), testis (40 per cent), peripheral blood (33 per cent), bone (29 per cent), nasal/paranasal sinuses region (23 per cent) and bone marrow (20 per cent). CNS prophylaxis is recommended to patients with an increased risk of CNS disease.     

Central nervous system involvement in patients with diffuse aggressive non-Hodgkin's lymphoma.

Central nervous system (CNS) involvement was evaluated in 277 consecutive patients with aggressive non-Hodgkin's lymphoma treated by the Nebraska Lymphoma Study Group. Three patients (1.1%) developed CNS involvement at presentation and 11 (4.0%) at relapse. The involvement was meningeal in 8 patients and documented by CSF cytology; it was parenchymal in 2 patients and proven by biopsy; and it was in the cauda equina in 1 patient at autopsy. Factors significantly associated with a greater likelihood of CNS relapse were age less than 60 years and epidural disease. Other factors, including tumor histology, extranodal disease at presentation, response to therapy, sex, and symptom type, were not significantly associated with a higher risk of CNS relapse. Survival of the patients presenting with CNS disease (6, 26, and 27+ months) was longer than patients whose CNS disease relapsed (median 2 months).     

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.     

Risk factors for intraocular involvement in patients with primary central nervous system lymphoma

To determine the risk factors for intraocular involvement in patients with primary central nervous system lymphoma (PCNSL), a retrospective chart review was performed on 136 patients who were pathologically diagnosed with PCNSL. The patients were investigated for demographics, clinical manifestation, and the profile of immunohistochemical tumor biomarkers, as well as for the presence of intraocular involvement of lymphoma at diagnosis or during follow-up. The mean age of the entire cohort was 58.6 ± 12.4 years, and the mean follow-up period was 31.1 ± 30.8 months. Twenty-nine (21 %) patients had an intraocular involvement, among which 20 (69 %) patients presented with intraocular involvement at diagnosis of PCNSL and 9 (31 %) patients developed intraocular involvement after a mean period of 32.4 ± 33.6 months. Of the patients with intraocular involvement, 8 (28 %) had no visual symptom at the diagnosis of ocular invasion. Between those with and without intraocular involvement, no significant differences were found with respect to the age, sex, and follow-up period as well as cerebrospinal fluid spread and bone marrow involvement. Among the immunohistochemical biomarkers, the Ki-67 proliferation index was significantly higher in patients with intraocular involvement than in patients without (P = 0.021), but the other investigated biomarkers did not show a significant difference between the two groups. A Ki-67 level ≥80 % was a risk factor for the intraocular involvement in patients with PCNSL (odds ratio, 2.63). Median overall survival was 39.0 months in the entire cohort and was not significantly different between those with and without intraocular involvement (P = 0.959).     

CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P =. 095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.     

Prognostic factors in non-Hodgkin's lymphoma.

There is an emerging consensus on the importance of identifying non-Hodgkin's lymphoma patients with different prognoses so that these patients can be optimally treated and the relative benefits of different therapeutic approaches can be adequately assessed. This review of recent publications on prognostic factors in lymphoma will summarize papers identifying: 1) clinical features associated with prognosis in specific subgroups of lymphoma patients; 2) the prognostic significance of pathologic and immunologic subclassification; 3) prognostic features predictive for relapse from complete response; and 4) newly identified prognostic features, including cytogenetic abnormalities, serologic parameters, and aberrant expression of adhesion molecules.     

71例原发颅内中枢神经系统DLBCL预后分析

目的 探讨原发颅内中枢神经系统弥漫性大B细胞淋巴瘤(DLBCL)的预后因素。 方法 回顾分析1991—2015年间收治的经病理和临床证实的 71例原发颅内中枢神经系统DLBCL临床资料。全组患者均进行了化疗,59例进行了放疗,化疗方案以HD-MTX (HD-MTX,66/71)为主,放疗方案以全脑放疗 ±局部推量为主。Kaplan-Meier法计算生存率,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。 结果 放化疗结束时 58例CR, 10例PR,3例PD。5年生存率为43%;5年无疾病进展率为34%。单因素分析显示年龄、KPS评分、单发与多发、是否放疗、放化疗完成时评价、有无复发是影响OS的因素(P=0.000~0.047),多因素分析显示年龄、KPS评分、有无复发是影响OS的因素(P=0.000~0.022)。单因素分析化疗方案、是否放疗、总放疗剂量、全脑剂量、放化疗完成时评价、有无复发是影响PFS的因素(P=0.000~0.028);多因素分析KPS评分、有无复发是影响PFS的因素(P=0.000~0.011)。 结论 年轻、KPS评分高、无复发患者总生存更好,单发、接受放疗、放化疗后疗效好的患者可能更好;KPS评分高、放化疗后疗效好、无复发患者PFS更好,接受含HD-MTX化疗、接受放疗、总的放疗剂量和全脑剂量越高患者PFS可能更好。化疗达CR后是否还放疗及放疗靶区、剂量需进一步研究。     

Predictive factors for central nervous system involvement in non-Hodgkin's lymphoma: significance of very high serum LDH concentrations

Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.     

Mantle zone lymphoma with central nervous system involvement

A 68-year-old man with a 7-year history of lymphocytosis and lymphadenopathy is described. Accelerated disease, indicated by bilateral optic nerve and cerebrospinal fluid involvement, prompted thorough histologic and immunologic assessment. Although initially believed to have chronic lymphocytic leukemia (CLL), results showed mantle zone lymphoma (MZL) with central nervous system (CNS) involvement. The authors believe that this represents the first case of MZL with CNS involvement.     

Endobronchial involvement with non-Hodgkin's lymphoma. A clinical-radiologic analysis

Based on experience with three cases of endobronchial non-Hodgkin's lymphoma and a review of cases previously reported, two patterns of lymphomatous involvement of airways are described. The Type 1 pattern is characterized by diffuse submucosal infiltrates occurring in the presence of intra- and extrathoracic lymphoma. In Type 2 cases, central airways are involved by a solitary mass in the absence of clinically apparent systemic lymphoma. The clinical-radiologic picture is characterized by signs of pneumonitis in Type 1 cases, while in Type 2 cases, signs of airway obstruction uniformly occur.     

Secondary involvement of the central nervous system in malignant non-Hodgkin's lymphoma. A study of 30 cases in a series of 498 patients

Of 498 patients with non-Hodgkin's lymphoma (NHL), 30 showed secondary central nervous system (CNS) involvement. Of these 30 patients, 26 had high-grade malignancy and 21 lymphoblastic lymphoma, mainly convoluted (n = 8) or Burkitt (n = 6) type according to the Kiel classification. In half of the 30 patients, CNS involvement was associated with progressive lymphoma. Bone marrow involvement was found in half of the patients before or at the time of the diagnosis of CNS involvement, which was 12 months (mean) after the diagnosis of NHL. Eight patients received CNS prophylaxis. Results of treatment for CNS involvement are poor (mean survival time from CNS involvement: 3.5 months). The Kiel classification allows good identification of patients at high risk of CNS lymphoma: systematic CNS prophylaxis is indicated only in the convoluted and Burkitt types. An efficient prophylaxis must be found and results must be confirmed by other studies.     

Elevated LDH and paranasal sinus involvement are risk factors for central nervous system involvement in patients with peripheral T-cell lymphoma

BackgroundThe incidence and risk factors of central nervous system (CNS) involvement in peripheral T-cell lymphomas (PTCLs) are still unclear.Patients and methodsWe analyzed 228 patients with PTCLs, excluding cases of extranodal natural killer/T-cell lymphoma and primary cutaneous T-cell lymphoma, by retrospectively collecting the clinical features and outcomes of the patients.ResultsTwenty events (8.77%, 20/228) of CNS involvement were observed during a median follow-up period of 13.9 months (range 0.03–159.43). Based on univariate analysis, elevated serum lactate dehydrogenase (LDH) level [P = 0.019, relative risk (RR) 5.904, 95% confidence interval (CI) 1.334–26.123] and involvement of the paranasal sinus (P = 0.032, RR 3.137, 95% CI 1.105–8.908) adversely affect CNS involvement. In multivariate analysis, both were independently poor prognostic factors for CNS relapse [elevated LDH level: P = 0.011, hazard ratio (HR) 6.716, 95% CI 1.548–29.131; involvement of the paranasal sinus: P = 0.008, HR 3.784, 95% CI 1.420–10.083]. The survival duration of patients with CNS involvement was significantly shorter than that of the patients without CNS involvement (P = 0.009), with median overall survival of 7.60 months (95% CI of 4.92–10.28) versus 27.43 months (95% CI of 0.00–57.38), respectively.ConclusionsElevated LDH level and involvement of the paranasal sinus are two risk factors for CNS involvement in patients with PTCLs. Considering the poor prognoses after CNS relapse, prophylaxis should be considered with the presence of any risk factor.     

Intrathecal chemotherapy alone is inadequate central nervous system prophylaxis in patients with intermediate-grade non-Hodgkin's lymphoma

Central nervous system (CNS) relapse of non-Hodgkin's lymphoma (NHL) is usually fatal despite therapy and effective prophylaxis is desirable. Patients at high-risk usually receive intrathecal (i.t.) prophylaxis, although its efficacy is unproven. We therefore analyzed the outcome of all patients with newly diagnosed "intermediate-grade" NHL receiving i.t. prophylaxis from 1991 to 1999. Twenty-six patients were identified and analyzed. All were free of CNS involvement at diagnosis with negative cerebrospinal fluid (CSF) cytology. Disease stage was IE in 7, and IV in 19, with a median of two extranodal sites involved. Serum lactate dehydrogenase was elevated in 65%, and the median International Prognostic Factors Index score was 3 (range 0-5). Anthracycline-based chemotherapy was used in all cases and included high-dose methotrexate +/- ara-C in six patients. The median number of i.t. treatments was 5 (range 1-12) and comprised methotrexate +/- steroid in 15, together with ara-C in 11. The actuarial 3-year CNS-relapse rate was 26 +/- 10%. Six CNS-relapses were observed and involved the spinal cord or brain parenchyma in two cases each, and the leptomeninges in four patients. Treatment-related variables associated with higher CNS-relapse rates (34-50%) were: delay of > or = 14 days from diagnosis to first i.t. injection, < 5 i.t. treatments, delay of i.t. prophylaxis until after attaining CR and systemic treatment lacking high-dose methotrexate +/- ara-C (each P < or = 0.17). I.t. CNS prophylaxis, as used here, was inadequate. Alternative approaches should be pursued.     

原发扁桃体非霍奇金淋巴瘤的预后因素

目的：评价原发扁桃体非霍奇金淋巴瘤（NHL）的肿瘤侵犯范围（T分期）和国际预后指数（IPI）的预后价值,并对早期患者提出治疗建议。方法：回顾分析306例原发扁桃体NHL,根据Ann Arbor分期,I期35例,II期178例,Ⅲ期49例,Ⅳ期44例,根据1997年AJCC TNM分期标准,TI 29例,T2 142例,T3 117例,T4 18例,I期单纯放射治疗12例,综合治疗23例,Ⅱ期单纯放射治疗57例,单纯化疗2例,综合治疗119例,Ⅲ,Ⅳ期以化疗为主,结果：T1,T2,T3和T4的5年癌症相关生存率（CSS）分别为73．8％,59．0％,56．5％和26．5％（P＜0．05）,IP1评分0分,1分和2或3分的5年CSS分别为69．9％,49．0％和25．0％（P＜0．01）,II期单纯放疗和综合治疗的5年无瘤生存率（DFS）分别为46．2％和60．4％（P＜0．05）,多因素分析证明,影响预后的因素有一般状态,B症状,Ann Arbor分期,T分期和IPI,结论：原发肿瘤T分期和IPI是扁桃体NHL重要的预后因素,综合治疗改善了II期扁桃体NHL的DFS。     

Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma

The authors describe the results of multimodality therapy in 27 patients with biopsy-proven primary central nervous system (CNS) lymphoma treated between 1976 and 1986. Treatment included surgical resection (15 patients), radiotherapy (27 patients), and chemotherapy (nine patients). Actuarial survival rates for the 27 patients at 1, 2, and 5 years after diagnosis were 70%, 54%, and 45%, respectively. Nine patients were recurrence-free at 8 to 106 months follow-up. A multivariate risk analysis identified five factors which had a favorable impact on survival: (1) age less than 60 years (P less than 0.02); (2) preoperative Karnofsky performance score greater than or equal to 70 (P less than 0.02); (3) presence of strictly hemispheric tumor (P less than 0.0003); (4) whole-brain radiation dose between 4000 and 5000 cGy (P less than 0.05); and (5) addition of chemotherapy to radiotherapy (P less than 0.002). Patients with complete tumor resolution on computed tomography 6 months after beginning treatment also had longer survival (P less than 0.01). The presence of malignant cells on cerebrospinal fluid cytologic examination correlated with an increased risk of distant metastasis (P less than 0.05). In those patients whose disease eventually recurred, the administration of an additional therapeutic modality significantly increased the length of postrecurrence survival (P less than 0.05). Although surgical resection provided no increase in survival, the addition of chemotherapy to postoperative cranial irradiation significantly enhanced the duration of survival. Our experience suggests that pretreatment clinical and diagnostic factors can help in predicting survival and in planning treatment.     

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...     

Efficacy and safety of liposomal cytarabine in lymphoma patients with central nervous system involvement from lymphoma

BACKGROUND:

Standard intrathecal chemotherapy for lymphomatous meningitis (LM) is limited by the short cerebrospinal half‐lives of the agents used, necessitating frequent administration. Liposomal cytarabine (DepoCyte) has an extended half‐life that permits administration at 2‐ to 4‐weekly intervals.

METHODS:

Patients with LM who underwent treatment with liposomal cytarabine at treatment centers in Spain between 2004 and 2007 were identified. Data on demographics, treatment, and outcomes were extracted from medical notes and entered, retrospectively, into a database for analysis.

RESULTS:

Data on 55 patients with lymphoma (mainly stage IV) and LM were entered into the database. Most patients (n = 36) had diffuse large B‐cell lymphoma. The median number of cycles of liposomal cytarabine received was 4 (range, 1‐10), and the median follow‐up period was 124 days. Complete and partial neurologic responses were achieved in 27 and 12 patients, respectively (overall response rate, 72%), all of whom also showed a cytological response, except for 5 with initially negative cytology. Median time to neurologic progression among responders was 105.5 days. Liposomal cytarabine was generally well tolerated; headache was the most commonly reported adverse effect (n = 17).

CONCLUSIONS:

Liposomal cytarabine is effective and well tolerated in the treatment of LM, and should be considered as an agent of choice for the treatment of this complication. Cancer 2009. © 2009 American Cancer Society.     

Patterns of central nervous system recurrence in patients with systemic human immunodeficiency virus-associated non-hodgkin lymphoma.

BACKGROUND: Central nervous system involvement is a common manifestation of non-Hodgkin lymphoma (NHL) in human immunodeficiency virus (HIV)-infected individuals. The purpose of this study was to review the frequency and pattern of neurologic manifestation of lymphoma in a cohort of HIV-infected individuals with systemic NHL. METHODS: Sixty-two patients with HIV-associated systemic NHL received infusional cyclophosphamide, doxorubicin, and etoposide. Five patients with lymphomatous meningitis at presentation received whole brain radiation therapy plus intrathecal chemotherapy (ITC). Of the remaining 57 patients, prophylactic ITC was recommended only for those patients with lymphomatous bone marrow involvement and/or high grade histology (N = 31). RESULTS: Thirteen patients (21%) had histologically documented (N = 6) or presumed (N = 7) central nervous system involvement, including 7 patients (11%) with meningeal lymphoma discovered either at presentation (N = 5) or soon after diagnosis (N = 2), and 6 patients (10%) with cerebral mass lesions at the time of disease recurrence consistent with parenchymal brain involvement. Five of six parenchymal brain recurrences occurred in the setting of progressive systemic disease. Four of 7 patients (57%) with meningeal lymphoma detected at presentation (N = 5) or within 3 months of presentation (N = 2) responded to therapy and survived >1 year. Of the 26 patients assigned to receive no prophylactic ITC, no patient developed an isolated meningeal recurrence and 1 patient developed an isolated parenchymal brain recurrence. CONCLUSIONS: The findings of the current study suggest that in patients with HIV-associated systemic lymphoma, meningeal lymphoma is potentially curable, parenchymal brain recurrence usually occurs in the setting of uncontrolled systemic disease, and prophylactic ITC may not be necessary for patients with intermediate grade histology and uninvolved bone marrow.     

Potential of chemo-immunotherapy and radioimmunotherapy in relapsed primary central nervous system (CNS) lymphoma

Five patients with relapsed PCNSL were given chemo-immunotherapy (rituximab followed by carboplatin and methotrexate) with osmotic blood-brain barrier (BBB) opening. Four patients achieved CR and one patient had stable disease. Two patients (2/5) had durable responses (survival: 230+, 122+, 82, 42, 38 weeks). One patient later received Indium-111-ibritumomab tiuxetan and Yttrium-90-ibritumomab tiuxetan intravenous, without BBB opening. There was good uptake of Indium-111 ibritumomab tiuxetan in tumor on SPECT scan after 48 h. Estimated radiation doses to brain around and distant from tumor were within safe limits. After Ytrium-90 ibritumomab tiuxetan there was CR in enhancing tumor where the BBB was leaky, but lesions occurred in other brain regions, where the BBB was intact during Yttrium-90 ibritumomab tiuxetan infusion. Imaging and dosimetry with Indium-111 ibritumomab tiuxetan and efficacy with Yttrium-90 ibritumomab tiuxetan suggest the need for future enhanced CNS delivery when using monoclonal or radiolabeled antibodies, as intravenous delivery alone may provide modest clinical benefit due to limited BBB permeability.