Increasing incidence and continued dismal outcome of primary central nervous system lymphoma in Norway 1989-2003 : time trends in a 15-year national survey

BACKGROUND: The incidence of primary central nervous system lymphoma (PCNSL) appears to be increasing in some countries, whereas it is stable in others. Many reports the last decades have suggested that there have been improvements in the treatment of PCNSL. The objective of this study was to analyze time trends in the incidence, clinical features, histologic diagnosis, treatment, and outcome of nonacquired immunodeficiency syndrome (non-AIDS) PCNSL in Norway from 1989 to 2003. METHODS: Patients were identified by a chart review of all patients who had a recorded diagnosis of PCNSL from 1989 to 2003 in The Norwegian Cancer Registry. The histologic and cytologic material from each patient was re-examined by pathologists. Time trends were analyzed according to year of diagnosis grouped into 3 5-year periods: 1989-1993, 1994-1998, and 1999-2003. RESULTS: There were 98 patients who had confirmed, newly diagnosed non-AIDS PCNSL in Norway from 1989 to 2003. The incidence rate increased during the consecutive 5-year periods from 0.89 per million during 1989 to 1993, to 1.74 per million during 1994 to 1998, and to 1.82 per million during 1999 to 2003 (P = .013). Diagnostic delay and overall survival did not improve with time. Survival decreased from 1999 to 2003 compared with survival from 1994 to 1998, which was explained in part by reduced performance status and fewer patients receiving combined chemotherapy and radiotherapy during 1999 to 2003. In multivariate analysis, age 相似文献   

Incidence trends and survival of penile squamous cell carcinoma in the Netherlands

We examined trends in the incidence and mortality, and described the survival of patients with penile squamous cell carcinoma in the Netherlands between 1989 and 2006. On the basis of nationwide population‐based data, 3‐year moving average European age‐standardized incidence and 10‐year relative survival estimates were calculated. Penile squamous cell carcinomas were categorized according to stage grouping based on the TNM classification. In the 17‐year study period, 2000 primary penile cancers were diagnosed in the Netherlands of which 1883 (94%) were squamous cell carcinomas. Median age at diagnosis was 68 years. The majority of patients (57%) were diagnosed with localized tumors (Stage 0 or I). The percentage of missing disease characteristics increased with increasing age. The 3‐year moving average incidence rate of patients with penile squamous cell carcinoma increased significantly from 1.4 per 100,000 person‐years in 1989 to 1.5 in 2006 with an estimated annual percentage of change of 1.3%. Ten‐year relative survival of patients according to the different stage groups was 93% for Stage 0, 89% for Stage I, 81% for Stage II, the 9‐year survival was 50% for patients with Stage III disease and a 2‐year survival of 21% for patients was found for Stage IV disease. Our study shows that the incidence rate of penile squamous cell carcinoma in the Netherlands has increased slightly, especially the incidence of carcinomas in situ. Patients with Stage III and IV tumors have poor survival.     

Incidence, clinical features, treatment and outcome of primary central nervous system lymphoma in Norway

The incidence of primary central nervous system lymphoma (PCNSL) has been reported to increase in some parts of the world, while being stable in other regions. In an attempt to characterize the incidence rate, clinical features, treatment, outcome, and prognostic factors of PCNSL in Norway, we report our experience in a large unselected series of patients. Clinical features, histological diagnosis, radiological findings, treatment, and outcome of all patients diagnosed with PCNSL in Norway in the years 1989-1998 were registered. During the 10-year period 58 new cases of histologically verified PCNSL were registered in Norway. The annual incidence rate of PCNSL was on average 1.34 cases per million people with a non-significant increasing trend (p=0.069). For patients diagnosed before death (n=45) the estimated survival following histological diagnosis was 55%, 47%, and 23% at 1, 2, and 5 years, respectively. In Cox-regression analysis age, WHO performance status and treatment had independent prognostic impact on survival. In the studied decade, there was a non-significant trend towards increased incidence of PCNSL, perhaps due to increased availability of diagnostic imaging, especially magnetic resonance imaging.     

Trends in survival of prostate cancer in southeastern Netherlands, 1971-1989

The increase in the incidence of prostate cancer observed over the past 2 decades is suggested to be largely due to increased detection of insignificant tumors. To explore this assumption, we investigated trends in survival of prostate cancer patients in southeastern Netherlands, an area with almost 1 million inhabitants, where the age-adjusted incidence of prostate cancer increased by 53% between 1971 and 1989, i.e., before the introduction of prostate-specific antigen testing. Survival was calculated for all patients registered in the Eindhoven Cancer Registry between 1971 and 1989 (n = 2,562). In spite of earlier diagnosis, survival barely changed during this time period. Five-year relative survival improved slightly from 53% [95% confidence interval (CI) 47%, 59%] in 1975-1979 to 56% (CI 51%, 61%) in 1985-1989. Stratified analyses suggested an improvement since 1980 for patients below 75 years with localized tumors but, despite possible stage migration, decreased survival for those with metastasized and/or poorly differentiated tumors. Patients below 75 years whose tumors were diagnosed unexpectedly during transurethral resection of the prostate (TURP) exhibited a relative survival of 85% 5 years and 68% 10 years after diagnosis. Less extensive application of TURP in The Netherlands might explain why our findings do not agree with those in Sweden and the United States. Inference from country-specific trends in survival appears not to be necessarily generalizable to other countries with a similar increase in the incidence of prostate cancer. We conclude from our results that earlier diagnosis of prostate cancer between 1971 and 1989 may be accompanied by an increased incidence of an aggressive variant.     

Trends in survival from primary central nervous system lymphoma, 1975-1999: a population-based analysis

BACKGROUND: The age-adjusted incidence of primary central nervous system lymphoma (PCNSL) has increased since the 1970s, and treatment for this disease has evolved considerably. The objective of this study was to examine time trends in overall survival and disease-specific mortality in a population-based cohort of patients with PCNSL. METHODS: We identified patients diagnosed with PCNSL from 1975-1999 in the Surveillance, Epidemiology, and End Results (SEER) cancer registries. To assess time trends, year of diagnosis was classified in 5-year intervals: 1975-1980, 1981-1985, 1986-1990, 1991-1995, and 1996-1999. Overall survival distributions were estimated via Kaplan-Meier methodology and a competing risk analysis was used to assess PCNSL-specific mortality. We used information on underlying cause of death to distinguish likely immunocompetent patients from those whose PCNSL was related to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). We also examined survival stratified by age at diagnosis. RESULTS: From 1975-1999, 2462 patients were diagnosed with PCNSL in SEER. Median survival was 4 months (95% CI 4, 5) for the entire cohort and 9 months (95% CI 8, 11) for the immunocompetent cohort (n = 1565). In the immunocompetent cohort, 965 of 1323 (73%) deaths were attributed to PCNSL. No significant time trend was observed in either overall or PCNSL-specific survival. CONCLUSIONS: Overall survival for patients with PCNSL has not improved consistently in the past three decades despite important therapeutic advances during this time. Although results from clinical trials suggest progress in the treatment of PCNSL, survival improvements are not reflected in this population-based cohort.     

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature

BackgroundCentral nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL).Patients and MethodsWe evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen.ResultsThe median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively.ConclusionIn this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.     

Incidence of primary cancer of the central nervous system in southeastern Netherlands during the period 1980-94

Objectives: Substantial increases in incidence and mortality rates for primary brain tumors have been reported in many, but not all, countries over the past several decades. We analyzed incidence rates for (potential) primary malignant central nervous system (CNS) tumors in an area (southeastern Netherlands) and during a period (1980-94) in which access to healthcare was good and computerized tomography (CT) was available. Methods: Data were obtained from the Eindhoven and Maastricht cancer registries, representing a population of 936,000 and 847,000 inhabitants, respectively. Cases were identified of primary CNS tumors (ICD-0 codes 191, 192, excluding lymphomas) and brain metastases from an unknown primary site (code 199) and data on mortality according to gender and region were provided by Statistics Netherlands. Results: Incidence rates in three-year periods of primary CNS cancer remained stable, also for patients aged 60 years and older. Mortality/incidence ratios ranged from 0.6 to 0.9. Although more CNS cancers were histologically verified in recent years, especially in the Eindhoven region, changes in diagnosis probably did not influence the overall trend of primary CNS cancer. Conclusions: Major changes in the incidence of the most common types of primary CNS cancers (i.e., high-grade astrocytomas) were unlikely in southeastern Netherlands.     

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.     

Prognosis for long-term survivors of cancer.

BACKGROUND: Many cancer patients who have already survived some time want to know about their prognosis, given the pre-condition that they are still alive. We described and interpreted population-based conditional 5-year relative survival rates. PATIENTS AND METHODS: The long-standing Eindhoven Cancer Registry collects data on all patients diagnosed with cancer in the southern part of the Netherlands. Patients aged 25-74 years, diagnosed between 1960 and 2004, were included. Conditional 5-year relative survival was computed for every additional year survived (follow-up period 1980-2004). RESULTS: For patients with colorectal cancer, cutaneous melanoma or stage I breast cancer, conditional 5-year relative survival was >95% after having survived 3-15 years. However, for stomach, lung, stage II or III breast, prostate cancer or Hodgkin lymphoma, conditional 5-year relative survival did not exceed 75-94%. Initial differences in survival at diagnosis between age, gender and stage groups largely disappeared after having survived for 5-10 years. CONCLUSION: Prognosis for patients with cancer generally improved with each year survived. Patients with colorectal cancer, cutaneous melanoma or stage I breast cancer hardly exhibit any excess mortality after 3-15 years, whereas for patients with other tumours survival remained poorer than for the general population. Insight into conditional survival is especially useful for (ex)patients, who may use this information to plan their remaining life.     

Management of Immunocompetent Patients With Primary Central Nervous System Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) is a non-Hodgkin lymphoma that arises within and is confined to the CNS. Recent data have suggested an increasing incidence in immunocompetent individuals, with a peak of incidence between 60 and 70 years of age. Patients with PCNSL present mostly with symptoms of increased intracranial pressure. The clinical management of these patients remains controversial, and the optimal treatment for patients with PCNSL has not yet been defined. Surgery, even if macroscopically radical, does not improve survival because of the multifocal and infiltrative nature of PCNSL; furthermore, the deep location of most of these tumors makes patients susceptible to serious and irreversible neurologic sequelae. Corticosteroids have a specific role in the treatment of patients with PCNSL, whose disease is sensitive to them as a chemotherapeutic agent. PCNSL is an extremely radiation-sensitive neoplasm; whole-brain radiation therapy plus corticosteroids was the first modality of treatment for patients with this neoplasm until 10 years ago, with a low cure rate and a high local recurrence rate. PCNSL is also a chemosensitive neoplasm; while the optimal choice, sequence, and combination of appropriate agents for efficacious treatment of patients with PCNSL has yet to be determined. An essential component of therapy must include an adequate drug delivery behind a normal blood-brain barrier. Methotrexate is the agent with the most proven activity in PCNSL. Combined-modality therapy has improved survival, but relapse is still common, and late neurologic toxicity is a significant complication, especially in older patients, who represent the majority of immunocompetent patients with PCNSL.     

Age, gender, and racial differences in incidence and survival in primary CNS lymphoma

Background:

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that accounts for ∼4% of newly diagnosed central nervous system (CNS) tumours. The objective of this study was to analyse the epidemiology, incidence, and outcome of these rare tumours.

Methods:

Primary brain and CNS lymphoma cases were identified from the Surveillance, Epidemiology, and End Results (SEER) research data sets for the years 1980–2008 for analysis of trends in incidence and survival. SEER^*Stat v. 7.0.4 software was used to analyse the data.

Results:

The overall incidence rate of PCNSL was 0.47 per 100 000 person-years. The incidence was significantly higher in males compared with females, blacks aged 0–49 years at diagnosis compared with whites, and whites aged 50 years and older at diagnosis compared with blacks. After a significant decline in incidence between 1995 and 1999, incidence rates rose slightly; those aged 75+ years at diagnosis had the most dramatic increase in incidence rates over time. Five-year survival rates were significantly higher in whites compared with blacks aged 0–49 years at diagnosis, but was primarily driven by white women aged 0–49 years.

Conclusion:

There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population. Survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.     

Changing incidence and survival in patients with aids-related non-Hodgkin's lymphomas in the era of highly active antiretroviral therapy (HAART)

To determine role of highly active antiretroviral therapy (HAART) and additional factors in incidence and outcome of patients with AIDS-related non-Hodgkin's lymphomas (NHL) we retrospectively analyzed 257 cases of AIDS-related NHL (24 low-grade, 168 high-grade B-cell, 6 high-grade T-cell, and 59 primary CNS lymphomas (PCNSL) among 2004 patients with HIV-infection treated at the University Hospital of Frankfurt, Germany from January 1983 to May 1999. Data were evaluated by univariate and multivariate analyses, using overall survival as end point. Patients received CHOP-like therapy as standard treatment. Until May 1999 incidence of all diagnosed cases of NHL was decreasing (1991-94: 14.2% versus 1995-5/99: 12.8%). Mainly, the incidence of low-grade NHL and PCNSL clearly decreased whereas the incidence of high-grade B-cell NHL increased compared to all diagnosed cases of NHL (1983-86: 53.3% versus 1995-5/99: 78.6%). One-year survival probability of all screened patients with AIDS related NHL was 54%, while 5-year survival rate remained 5%. We found age <25 years, development of NHL in the years before 1990, IVDU, CD4 counts <150/microl, PCNSL as well as NHL as the AIDS index disease, to be highly significant independent predictors of poor survival, including increased hazard ratios. In the era of HAART incidence of NHL is decreasing, mainly the incidence of low-grade NHL and PCNSL. Overall survival of patients has been prolonged with HAART. This development is mainly due to improvement of antiretroviral therapy, rather than to any fundamental changes in the chemotherapeutic treatment of NHL. Therefore, new treatment approaches for AIDS-related NHL should focus on more efficient antiretroviral therapy in association with combination chemotherapy.     

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.     

34例原发性中枢神经系统恶性淋巴瘤临床分析

目的:分析免疫功能正常的中国人原发性中枢神经系统淋巴瘤(PCNSL)的临床资料,探讨PCNSL的临床特征,评价大剂量甲氨蝶呤(HD-MTX)加全脑放疗(WBRT)治疗PCNSL的疗效。方法:回顾性分析34例经病理证实的PCNSL患者的临床资料以及治疗效果,Kaplan-Meier法分析患者生存期。结果:34例PCNSL患者中B细胞淋巴瘤31例(91.2%),T细胞淋巴瘤3例(8.8%);所有患者治疗后评价完全缓解率(CR)41.2%,2年生存率60.2%;病理类型和是否接受HD-MTX加放疗是影响PCNSL生存期的主要原因(P<0.05)。结论:PCNSL以颅内高压为主要表现,B细胞亚型占绝对优势,具有独特的预后因素,HD-MTX联合放疗是PCNSL有效的治疗方法。     

Clinicopathological Features, Survival And Prognostic Factors Of Primary Central Nervous System Lymphomas: Trends in Incidence of Primary Central Nervous System Lymphomas and Primary Malignant Brain Tumors in A Well-Defined Geographical Area; Population-Based Data from the Danish Lymphoma Registry, Lyfo, And the Danish Cancer Reistry

It has been claimed that Primary Central Nervous System Lymphoma! (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extrancdal non-Hcdgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate I I-year period from 1st January 1983 to 3 1st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate I I-year period 3 124 new cases of NHL were registered. Of these, I 152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for4.2% ofextranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was I .56 cases per million population (age range: 15-85 yrs, median: 62 yrs, MIF ratio: I).In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had 6-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WkRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%. 38% and 26% at I, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL performance score 2 2 (pc 0.001. RR = 5.8     

Increased but low incidence and poor survival of malignant mesothelioma in the southeastern part of The Netherlands since 1970: a population-based study.

Changes in the incidence and survival rates for malignant mesothelioma in the southeastern part of The Netherlands since 1970 were investigated, using data from the Eindhoven Cancer Registry (ECR). The exposure to asbestos in this area is presumed to be limited. Most of the mesotheliomas occurred in the pleura, where there were 119 (88%) against 15 (11%) in the peritoneum and two in the tunica vaginalis testis. Compared to other European countries, the incidence rate for the southeastern part of The Netherlands was fairly low in the second half of the 1980s. Between 1975 and 1994 the age-adjusted incidence rates (ESR) for pleural mesothelioma increased twofold (from 10 to 19 per one million person-years among men and from 2.4 to 3.8 among women). The rate for peritoneal mesothelioma remained constant. The overall relative 0.5-, 1-, and 3-year survival rates remained 68, 42, and 8%, respectively. The fourfold higher incidence rate for men compared with women reflects the fact that mesothelioma is mainly an occupational disease. In view of presumed limited exposure to asbestos and small geographical variation, the incidence of mesothelioma in the southeastern part of The Netherlands will probably remain low, despite an increase in the past decades.     

Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10.

PURPOSE: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL. PATIENTS AND METHODS: We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m(2), vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT. RESULTS: Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P <.001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died. CONCLUSION: This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.     

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa,Busulfan, and Cyclophosphamide Conditioning Regimen

BackgroundHigh-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.Patients and MethodsA retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).ResultsThe 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.ConclusionHDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.     

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.