Human immunodeficiency virus-related primary central nervous system lymphoma: factors influencing survival in 111 patients

BACKGROUND: The current study evaluated factors influencing survival in patients diagnosed with human immunodeficiency virus (HIV)-related primary central nervous system lymphoma (PCNSL), with a focus on the effects of therapeutic radiotherapy (RT) and highly active antiretroviral therapy (HAART). METHODS: A retrospective chart review of patients with a diagnosis of HIV-related PCNSL at one of five university hospitals between 1987 and 1998 was performed. Clinical details including antiretroviral agent use, brain imaging scan results, RT use, and survival outcomes were recorded. RESULTS: One hundred eleven patients with HIV-related PCNSL were identified. The annual incidence decreased significantly between 1992 and 1995 and between 1996 and 1998 (P = 0.04). The median survival period was 50 days (mean, 109 days; range, 4-991 days), with improved survival for patients diagnosed after 1993. Patients treated with two or more antiretroviral agents had improved survival (P = 0.01), as did patients who received RT (P < 0.0001). For patients who received RT, completion of the prescribed course and treatment to > or = 30 Gray (Gy) independently predicted a more favorable outcome. RT used in conjunction with antiretroviral therapy involving two or more agents had an additive positive effect on survival. For patients who did not receive RT, poor performance status and encephalopathy predicted a shorter survival duration. CONCLUSIONS: The results of the current study suggest that HAART and treatment with RT to > or = 30 Gy improve survival for patients with HIV-related PCNSL. This combination of therapies may provide a standard of care as the basis for further trials of chemotherapy, novel adjunctive treatment, and quality of life assessment.     

Biologic aspects of human immunodeficiency virus-related lymphoma.

A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. In the vast majority of cases, these lymphomas are highly aggressive B-cell, non-Hodgkin's lymphoma of intermediate or high grade of malignancy. AIDS-associated non-Hodgkin's lymphoma are histologically classified as small noncleaved cell lymphoma, large cell immunoblastic plasmacytoid lymphoma, or large noncleaved cell lymphoma. Host factors predisposing to lymphoma development in AIDS patients include decreased immunosurveillance as well as human immunodeficiency virus-induced chronic perturbation of the immune system leading to cytokine overproduction and increased B-cell stimulation. These alterations are associated with the development of multiple oligoclonal B-cell expansions, which are characterized by persistent generalized lymphadenopathy. The presence of Epstein-Barr virus within a persistent generalized lymphadenopathy clone further increases the risk of its neoplastic transformation. The appearance of non-Hodgkin's lymphoma is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal Epstein-Barr virus infection, c-myc rearrangements, Ras mutations, and p53 inactivation. The number and type of lesions varies among the different types of AIDS-non-Hodgkin's lymphoma, defining multiple alternative molecular pathways in AIDS-associated lymphomagenesis.     

Clinical aspects of human immunodeficiency virus-related lymphoma.

As patients with human immunodeficiency virus infection live longer because of better antiretroviral therapy and infection prophylaxis, the incidence of non-Hodgkin's lymphoma has increased. The risk increases inversely with CD4 count--the most widely used surrogate marker for progressive immune suppression. Zidovudine itself does not appear to be a risk factor. Patients frequently present with extranodal advanced disease. The central nervous system is the primary site in 10% to 20% of cases. Important prognostic factors are performance status, a prior history of acquired immunodeficiency syndrome, and bone marrow involvement. Therapy is complicated by underlying immunosuppression, opportunistic infection, and poor bone marrow reserve. Progress has been made using colony-stimulating factors and less intensive chemotherapy regimens in systemic non-Hodgkin's lymphoma. Treatment of primary central nervous system lymphoma with radiation therapy has not improved survival.     

原发性胃肠道恶性淋巴瘤术后生存期的影响因素及TNM分期对远期生存的预测价值分析

目的 探讨原发性胃肠道恶性淋巴瘤术后生存期的影响因素及TNM分期对远期生存的预测价值。方法 纳入我院收治的原发性胃肠道恶性淋巴瘤患者102例,对患者临床资料进行回顾性分析。通过电话随访明确其术后5年内的生存情况与生存时间,采用Cox回归分析观察原发性胃肠道恶性淋巴瘤患者生存期的影响因素,利用Kaplan-Meier绘制生存曲线图分析TNM分期对患者生存期的预测价值。结果 在102例患者中,死亡41例,占全部病例的40.20%;生存组无远处转移、TNM分期Ⅰ~Ⅱ期、Lugano分期Ⅰ~Ⅱ期占比高于死亡组,差异有统计学意义(P＜0.05);以TNM进行分期时,患者Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期5年内的生存率分别为54.10%、21.31%、16.39%、8.20%。以Lugano进行分期时,患者Ⅰ期、Ⅱ期、ⅡE期、Ⅳ期5年内的生存率分别为52.46%、22.95%、13.11%、11.48%,经Cox回归分析提示远处转移、TNM分期、Lugano分期与患者生存期有关(P＜0.05);TNM分期对患者远期生存率的预测优于Lugano分期。结论 胃恶性淋巴瘤患者远期生存期的影响因素包括远处转移、TNM分期以及Lugano分期,与Lugano分期比较,TNM分期对远期生存期的预测效果更理想。     

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.     

Prognostic and predictive factors in prostate cancer.

Prostate cancer is a major public health problem in the Western world, and the second most common male malignancies in the European Union. Detection of the disease is possible at an early stage, using serum prostate specific antigen measurement and prostatic biopsies. To date, however, screening for prostate cancer has not been shown to be of benefit to patients in improving outcome. This is compounded by uncertainties surrounding treatment efficacy, as more men appear to die with prostate cancer than from it. Studies addressing these issues are underway in Europe and the U.S.A.Clinicians are currently unable to advise their patients with any degree of certainty as to the appropriateness of treatment for prostate cancer, because of their inability to differentiate tumours that will progress from those that will remain quiescent. This article reviews the various clinical, pathological and experimental markers available, and their value in providing prognostic information, which may assist clinicians and patients in making management decisions. Further research is still required to understand the biological behaviour of prostate cancer and to assess the value of screening and treatment efficacy in order to advise patients, clinicians and health care systems accordingly.     

Prognostic and predictive factors in breast cancer.

Around 570 000 women develop breast cancer worldwide. In the U.K. it affects 33 000 women and causes 16 000 deaths each year. Treatment of early breast cancer is surgical, comprising breast conserving surgery (followed by radiotherapy) for small unifocal tumours, or mastectomy for larger or multifocal tumours.Survival of patients with breast cancer depends on two different types of prognostic factors: tumour size reflecting how long the tumour has been present, and biological factors (i.e. grade) which represent tumour aggressiveness. In women with a tumour that has adverse features predicting early recurrence (i.e. lymph node positivity, large size, high grade) adjuvant systemic chemo- or hormonal therapy is given to reduce the risk of relapse. Chemotherapy is given to pre-menopausal women for oestrogen receptor negative post-menopausal breast cancer, whereas hormone therapy is reserved for oestrogen receptor positive cancer.Since 50% of patients will never relapse, identification of which women are at high risk of recurrence is necessary so as to offer treatment with adjuvant therapy. The use of hormone therapy and chemotherapy has been aided by factors predicting the likelihood of response, e.g. oestrogen receptor status. The value of newer prognostic and predictive markers is addressed.     

Prognostic factors for pleural lymphoma patients.

Prognostic factors in 47 patients with pleural lymphocytic lymphoma developing in chronic tuberculous pyothorax were evaluated using Cox's proportional hazards model. There were 41 men and six women, aged 44-80 (median 61) years. Approximately 70% of the patients had localized disease in Stages I and II, and 30% advanced disease in Stages III and IV. Histologically, 27 patients had the diffuse large, immunoblastic type and 12 had others. In the other seven patients, histological subtyping of the lymphocytic lymphoma was impossible because of degenerative or necrotic changes in the histologic specimens. A diagnosis of lymphocytic lymphoma of B-cell type was made in one case using combined cytologic and surface maker findings on a cell suspension. In addition, immunologic and immunohistochemical studies revealed another 40 cases to be proven B-cell lymphomas. Poor performance status and elevated levels of BUN and GPT were significantly associated with shortened survival in a Cox's proportional hazards model. A poor performance status and high levels of serum BUN and GPT suggested a marked deterioration in a patient's condition. When compared with previous literature describing prognostic factors in patients with B-cell lymphomas and with lymphocytic lymphomas with unfavorable histologies or associated with long-standing inflammations, the only common prognostic factors was performance status. The significance of primary site in predicting survival from lymphocytic lymphoma is discussed.     

EB病毒相关的人类免疫缺陷病毒阴性浆母细胞淋巴瘤的临床病理分析

目的 探讨人类免疫缺陷病毒（HIV）阴性且无免疫缺陷的浆母细胞淋巴瘤（PBL）的临床病理特征,提高对这组疾患的认识.方法 回顾性分析6例无免疫缺陷且HIV-PBL的组织学特点,原位杂交染色检测EB病毒（EBV）感染状态.分别采用免疫组织化学SP法及荧光原位杂交（FISH）技术检测PBL的免疫表型、EBV潜伏类型,探索myc基因的易位.结果 HIV-PBL表现为浆母细胞样或免疫母细胞样细胞的单一增生,可见瘤巨细胞及坏死;背景反应细胞少,核分裂象较多.所有病例都有EBV感染,潜伏类型为Ⅰ型（LMP1^-及EBNA2^-）.肿瘤细胞表达B细胞终末分化阶段的表型CD20^-/CD3^-/CD1386＋/Kappa＋或Lambda^＋.6例HIV-PBL均为老年患者（中位年龄69.5岁）,男女各3例;结外及口腔外侵犯率高,分别为6、5例.中位生存期为25.5个月.此外,3例患者具有免疫球蛋白重链（IgH）与myc基因易位.结论 HIV-PBL是一组独立疾患,具有无HIV感染、老年人、EBV阳性、结外及口腔外侵犯率高等特点,应与HIV＋的PBL相区别.     

滤泡性淋巴瘤预后因素的研究

滤泡性淋巴瘤(follicular lymphoma,FL)是一种起源于滤泡生发中心B细胞的淋巴瘤,其发病率在美国和西欧最高,而在亚洲和发展中国家的发病率相对较低。FL主要累及淋巴结,通常表现为无痛性多发淋巴结肿大。原发于淋巴结外的FL常见于胃肠道、软组织、乳腺及眼眶附属器。FL患者多表现为惰性临床过程,总生存率较高,但多数患者仍会复发或进展。回顾FL的预后因素,为指导患者的临床治疗提供理论依据。     

Prognostic factors of malignant lymphoma

Advances in staging and more refined radiation techniques and the combination chemotherapy have lead marked improvement of survival of patients with Hodgkin's disease and non-Hodgkin's lymphoma. The important prognostic factors used for choosing treatment programs are stage, histology, tumor bulk and the site of involvement for patients with early stage disease. Tumor bulk is considered as an important variable when patients are treated with radiation therapy alone. However, aggressive staging and effective therapy tend to obscure the differences in survival and relapse-free survival that would be observed in untreated patients and may be difficult to identify prognostic factors.     

Human immunodeficiency virus associated lymphoma

PURPOSE OF REVIEW: Human immunodeficiency virus (HIV) infection is known to be associated with an increased risk of systemic nonHodgkin lymphoma, Hodgkin disease, and primary central nervous lymphoma (PCNSL). The purpose of this review is to highlight recent advances in the diagnosis and management of lymphoma occurring in patients with HIV infection. RECENT FINDINGS: Lymphoma occurring in patients with HIV infection has been associated with a very poor prognosis. Recently reported studies have provided new information regarding the influence of highly active antiretroviral therapy (HAART) on the development and clinical presentation of lymphoma, the feasibility of combining HAART with standard chemotherapy, the molecular classification of lymphoma, the role of rituximab in the management of lymphoma, and the use of novel treatment strategies for the treatment of Hodgkin disease. SUMMARY: The improved prognosis for patients with HIV-associated lymphoma in the post-HAART era indicates that therapeutic interventions may be potentially curative, and represent a shift away from therapeutic nihilism and reduced-intensity treatment approaches that have been employed in the recent past.     

Prognostic factors in survival of bladder cancer.

Clinical and pathologic data of 36 patients with transitional cell carcinoma of the bladder were investigated to determine the significance on patient survival of these factors: pathologic grade and stage; the immunohistochemistry of eight cell and tumor markers; nuclear DNA flow cytometric parameters; and patient smoking status. The bivariate and multivariate statistical analysis significantly correlated patient survival rates with the immunohistochemical expression of blood group, isoantigens A (P less than 0.05), O(H) (P = 0.001), the oncogene-related protein ORP-p21 (P less than 0.05), the pathologic grade and stage (P = 0.002), and the tumor DNA ploidy (P less than 0.05). Smoking status correlated aneuploidy (P less than 0.05) and tumor expression of ORP-p21 (P less than 0.05) with the patient survival rate. Despite the relatively small number of patients in this study, the results suggest that the clinicopathologic variables are significant factors in survival of bladder cancer.     

Prognostic factors in non-Hodgkin's lymphoma

The results obtained with the various types of treatment in non-Hodgkin's lymphoma are reviewed and the data from the recent EORTC trials are summarized. In patients with Stage I follicular histology, regional radiotherapy (RT) alone gives excellent results. The long-term relapse-free survival (RFS) is high and relapsing patients can be rescued by aggressive combination chemotherapy; initial chemotherapy with CVP improves RFS but not total survival (TS). In patients with Stage I diffuse histology, the long-term survival is less satisfactory. CVP chemotherapy does not improve either RFS or TS; therefore if adjuvant chemotherapy is justified, it should be more aggressive than CVP. In patients with Stage II follicular type, regional radiotherapy alone gives good results. The addition of abdominal bath irradiation to regional RT increases RFS but not TS. After relapse, patients can be rescued by combination chemotherapy. In patients with Stage II diffuse histology, extended RT followed by CVP gives poor results and RT should be combined with more aggressive combination CT; the preliminary results of an integrated alternating regimen being excellent. In patients with Stage III and IV follicular type, the 8 year TS of patients treated with combination CT regimen (CHVP) followed by localized irradiation is approximately 55%, however the indications for the various types of treatment are still unclear. In patients with diffuse Stage III and IV, the results obtained with a combination CT regimen (CHVP) are still unsatisfactory, but are better in patients treated by a more aggressive CT regimen (CHVP-Bleo-VCR). Therefore aggressive CT associated with localized irradiation appears to be the best treatment. Further research should aim to identify the optimal combination CT regimen. In patients with high grade lymphomas who have relapsed the use of bone marrow autografts will be investigated. The present data show that besides histological type and age, the main prognostic factor is total tumor body burden as assessed by clinical stage, number of involved lymph node areas, and bulk of the disease. The study of the biological characteristics of the disease may provide more powerful prognostic indicators.     

Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients.

BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. CONCLUSIONS: The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used.     

侵袭性非霍奇金淋巴瘤预后相关因素分析

目的研究探讨侵袭性非霍奇金淋巴瘤的预后影响因素。方法回顾性分析137例侵袭性非霍奇金淋巴瘤的临床特征,结合随访资料,应用SPSS 10.0统计软件进行生存分析,并对其预后影响因素进行多因素分析。结果放化疗后达CR者35例(25.5%),其中近期CR 31例(22.6%), PR 67例(48.9%),SD 6例(4.3%),PD 29例(21.2%),总有效率为74.5%。4年总生存率为70.8%,4年无复发生存率为42.7%。Cox模型多因素分析显示,临床分期为Ⅲ～Ⅳ期、PS评分≥2分、累及淋巴结外病变数≥2个与预后关系密切,具有统计学意义。结论侵袭性非霍奇金淋巴瘤通过放化疗综合治疗,生存率有了较大提高。对于不同类型的NHL如何实施个体化的治疗方案,仍需进一步探讨。     

Chemotherapy combined with zidovudine and GM-CSF in human immunodeficiency virus-related non-Hodgkin's lymphoma

OBJECTIVE:: The treatment of patients with non-Hodgkin's lymphoma relatedto the human immunodeficiency virus (HTV-NHL) is complicatedby the underlying acquired immunodeficiency syndrome (AIDS).Patients without adverse prognostic factors (no AIDS prior tolymphoma, CD4+ lymphocyte counts greater than 100 x 106/l andgood performance status) can be cured of lymphoma and experiencelong-term survival. Our previous study with the intensive chemotherapyLNH84 regimen yielded a 63% complete response (CR) rate butmedian survival was only nine months, half of the patients diedof AIDS and the other half of their lymphoma. We report herethe results of a phase II study combining the same chemotherapywith zidovudine and GM-CSF. Our goal was to improve the treatmentoutcome over that of our previous study; GM-CSF was expectedto decrease the hematological toxicity of chemotherapy and thuspermit a dose intensity increase, while zidovudine was supposedto slow down the evolution of AIDS. DESIGN AND SETTING:: a phase II non-randomized prospective clinical trial in 7 centres. PATIENTS AND METHODS:: Thirty-two consecutive adult pa-tients presenting HTV-NHL andperformance status of less than three without active opportunisticinfection underwent three cycles of doxorubicin 75 mg/m2, cyclophosphamide1,200 mg/m2, vindesine 2 mg/m2 for two days, bleomycin 10 mgfor two days and prednisolone 60 mg/m2 for five days (ACVB).Chemotherapy was associated with zidovudine (5 mg/kg/d) andGM-CSF (5 ng/kg/d). The induction phase was followed by a four-monthconsolidation phase. RESULTS:: CR and PR > 75% were observed in 56% of patients; 25% ofthe patients died during the induction phase. These resultswere analogous to those of the previous study (63% and 14%,respectively). Neither hematological tolerance nor dose intensitywere improved. With a mean follow-up of 23.5 months, mediansurvival was 6.7 months. The rate of non-NHL AIDS-related deathduring CR was not reduced (22% in our study vs. 16% in our previousone). CONCLUSIONS:: GM-CSF failed to reduce significantly the cumulative hematologicaltoxicity of chemotherapy and zidovudine. New antiviral agentswithout hematological toxicity would perhaps be useful in thissetting. AIDS, chemotherapy, granulocyte-macrophage colony-stimulating factor, HIV, lymphoma, zidovudine