非霍奇金淋巴瘤中枢神经系统累及早期预防的研究进展

中枢神经系统（CNS）累及是非霍奇金淋巴瘤（NHL）的严重并发症,转归极度不佳。大多数病例CNS复发表现为软脑膜病变,在自然病程的早期即发生脑脊液播种,所以CNS预防需在最初治疗时进行。因为NHL患者CNS复发率相对低（5%-7%）,不同类型侵袭性NHL患者CNS预防仍有争议,最佳的治疗和方案尚不一致。明确侵袭性NHL患者CNS复发的危险因素有助于确定CNS预防患者亚群。由于目前CNS预防的措施尚欠一致和极少高质量验证,为预防治疗的过度需进行充分的设计和随机对照试验。     

非霍奇金淋巴瘤中枢神经系统累及早期预防的研究进展

中枢神经系统(CNS)累及是非霍奇金淋巴瘤(NHL)的严重并发症,转归极度不佳。大多数病例CNS复发表现为软脑膜病变,在自然病程的早期即发生脑脊液播种,所以CNS预防需在最初治疗时进行。因为NHL患者CNS复发率相对低(5%-7%),不同类型侵袭性NHL患者CNS预防仍有争议,最佳的治疗和方案尚不一致。明确侵袭性NHL患者CNS复发的危险因素有助于确定CNS预防患者亚群。由于目前CNS预防的措施尚欠一致和极少高质量验证,为预防治疗的过度需进行充分的设计和随机对照试验。     

原发性睾丸淋巴瘤的研究进展

原发性睾丸淋巴瘤(PTL)是一种罕见的结外非霍奇金淋巴瘤(NHL),占NHL的1％～2％.最常见的病理学类型为弥漫大B细胞淋巴瘤(DLBCL),少见类型为套细胞淋巴瘤、NK/T细胞淋巴瘤及其他T细胞淋巴瘤等.最典型的症状表现为无痛性单侧睾丸肿胀,可持续数周至数个月.PTL的预后极差,常出现中枢神经系统(CNS)及对侧睾丸复发.联合治疗方案包括腹股沟睾丸切除术、蒽环类药物为基础的化疗、对侧睾丸及受累野放疗和CNS预防治疗.目前临床上对PTL的预后指标、是否加用利妥昔单抗、放疗的价值及预防CNS复发的最佳策略等尚存在争议.文章针对这些问题进行综述.     

中枢神经系统骨髓瘤

多发性骨髓瘤（MM）累及中枢神经系统（CNS）十分罕见,约见于1％的MM患者。概述文献中报道的109例CNS骨髓瘤（CNSMM）的临床与实验室特征和治疗安排。CNSMM具有广谱的神经学症状和体征。迄今尚无CNSMM的治疗指南可采用,导致治疗安排变动较大。选择包括鞘内化疗（IT）、系统化疗（SC）、颅照射（CI）或其联合治疗。CNSMM的预后仍然不佳,从诊断至死亡的中位数总生存期为2．0个月（范围0．1～25个月）。与无CI治疗患者相比,包含CI治疗的患者生存期显著延长（P=0．004）。     

原发中枢神经系统弥漫大B细胞淋巴瘤临床特征及预后分析

目的：探讨原发中枢神经系统弥漫大B细胞淋巴瘤（PCNS DLBCL）的临床特征及预后相关因素。方法回顾性分析经病理确诊的70例PCNS DLBCL患者临床病理资料,并对66例可随访患者进行生存及预后分析。结果70例PCNS DLBCL患者中位发病年龄57岁,男女比例1.3∶1,就诊前病程小于2个月者54例（77.1%）。伴颅内高压症状44例（62.9%）,伴肢体无力或偏瘫症状26例（37.1%）。多发病灶37例（52.9%）,幕上59例（84.3%）,累及深部脑组织46例（65.7%）。66例随访患者中,对症姑息治疗7例,单纯手术23例,单纯放疗6例,单纯化疗9例,放化疗联合21例。随访6～96个月,全组中位生存期为9个月（95%CI 1～16个月）,2年生存率36.1%。对症姑息组中位生存期为2个月,单纯手术组中位生存期为3个月。接受放疗、化疗或放化疗联合组中位生存期为33个月（95%CI 22～43个月）,2年生存率56.9%。 Cox多因素回归分析显示,累及深部脑组织（P＝0.04）和未行放化疗（P＝0.00）是预后不良因素。结论 PCNS DLBCL为高度恶性肿瘤,进展迅速;单纯手术治疗效果差,生存期短;累及深部脑组织患者预后差;放疗、化疗及放化疗联合能显著改善患者的预后。     

10例原发性卵巢淋巴瘤临床分析

目的探讨原发性卵巢淋巴瘤（primary ovarian lymphonla,POL）的临床表现、诊断、治疗及预后。方法对10例POL患者的临床资料进行回顾性分析。根据AnnArbor分期法,ⅡE期2例,ⅣE期8例。,所有病例均为B细胞来源的非霍奇金淋巴瘤（non—Hodgkin’s lymphoma,NHL）。7例弥漫大B细胞淋巴瘤（diffuse large B—cell lymphoma,DLBCI．）中,1例部分呈Burkitt样分化,1例部分呈免疫母细胞分化;2例为未进一步细分的B细胞来源的NHL;1例为边缘带B细胞淋巴瘤。,10例患者均采用手术、化疗、放疗联合的综合治疗,3例患者行高剂量化疗及自体造血十细胞移植。结果中位随访期32．8个月。3例患者至随访结束时仍无病生存。中位无进展生存期（progression-free survival,PFS）为20．6个月（4．8-95．0个月）,中位总生存期（overall survival,os）为33．7个月（6．8～95．0个月）。结论POL临床表现无特异性,病理类型以DLBCL为主,临床分期多为晚期,临床上均采用手术、放疗、化疗联合的综合治疗。     

左旋门冬酰胺酶联合DICE方案治疗复发难治性非霍奇金淋巴瘤的疗效和安全性

 【摘要】　目的　探讨左旋门冬酰胺酶（L-Asp）联合DICE方案治疗复发难治性非霍奇金淋巴瘤（NHL）的疗效和安全性。方法　31例复发难治性NHL患者接受L-Asp联合DICE方案治疗,每位患者计划接受2～6个周期化疗。结果　在所有可评估的31例患者中,11例（35.5 %）完全缓解（CR）,14例（45.2 %）部分缓解（PR）,2例稳定,总有效（CR+PR）率为80.7 %。有效患者中位生存期为8个月（2～30个月）。全组患者预计1年生存率为43.3 %,2年生存率为32.5 %。主要不良反应为骨髓抑制、消化道反应、变态反应和水肿。治疗期间未观察到治疗相关性死亡。结论　L-Asp联合DICE方案治疗复发难治性NHL是有效和安全的。     

超敏C反应蛋白对非霍奇金淋巴瘤的预后评估作用

  目的  探讨超敏C反应蛋白（high sensitivity-C reactive protein,Hs-CRP）水平与非霍奇金淋巴瘤（non-Hodgkin lympho- ma,NHL）患者预后的关系。   方法  收集85例NHL患者的临床资料,中位随访14（1~59）个月,通过与已知的预后参数进行对比,探讨Hs-CRP对该疾病预后的预测价值。   结果  治疗前血清基础Hs-CRP水平≥4 mg/L较Hs-CRP水平 < 4 mg/L患者的无病进展生存期（progression free survival,PFS）更短（P < 0.05）,Hs-CRP水平≥4 mg/L较Hs-CRP水平 < 4 mg/L患者的总生存期（overall survi- al,OS）亦更短（P < 0.05）。治疗后早中期Hs-CRP水平与OS、PFS无显著相关性（P>0.05）。Cox多因素分析显示,治疗前血清基础Hs-CRP可作为NHL患者复发以及生存的一个重要预后参数（P < 0.05）。   结论  治疗前基础Hs-CRP水平可作为NHL患者预后的一个重要依据。      

92例非霍奇金淋巴瘤临床与预后分析

目的：分析非霍奇金淋巴瘤（NHL）的预后相关因素，以及不同治疗方法的预后。方法：对本院就治的92例非霍奇金淋巴瘤患者进行回顾性研究．采用Kaplan-Meier法分析患者治疗后的生存期，不同治疗方法患者生存期的差异性；采用Cox比例风险模型分析影响预后的因素，结果：全组2、5年无病生存率分别为68％和51％，5年CSS为55％。单因素分析表明，影响NHL的预后因素主要为Ann Arbor分期、B组症状、LDH、IPI预后指数和年龄。国际预后指数，低危（0～1分）、中低危（2分）、高中危（3分）和高危（4～5分）5年生存率分别为60％、62％、42％和33％。从不同分期治疗方法分析预后，Ⅰ、Ⅱ期全组病例单纯手术、单纯化疗和综合治疗的5年生存率分别为19％、72％和68％．综合治疗、单纯化疗生存率优于单纯手术组。Ⅲ、Ⅳ期全组病例单纯手术、单纯化疗和综合治疗的5年生存率分别为50％、35％和60％，综合治疗、生存率优于单纯化疗。结论：非霍奇金淋巴瘤患者的长期生存与多种因素密切相关，合理检测、调控相关因素可延长患者生存期。不同治疗方法可影响患者的预后．合理评估影响预后的因素，制定合理、有效的治疗可以延长患者的生存。     

原发性胃黏膜相关淋巴组织淋巴瘤60例临床分析

目的探讨原发性胃黏膜相关淋巴组织淋巴瘤的诊断、治疗、预后的特点。方法对1999年1月至2007年12月间收治的60例胃黏膜相关淋巴组织淋巴瘤患者的资料进行了回顾性研究,对临床分期、肿瘤大小、浸润深度、手术等指标做单因素和多因素分析。结果本组51例获得随访,平均随访时间39.7个月（1～93个月）。全组1,3,5年的总体生存率分别为80.3%、73.3%和68.1%,平均生存期67个月。全组1,3,5年的无病生存率分别为64.6%、62.2%和62.2%,平均无病生存期59个月。ⅠE期的5年生存率为86.7%,平均生存期82个月;ⅡE期的5年生存率为50%,平均生存期56个月;Ⅲ～Ⅳ期的5年生存率为42.9%,平均生存期26个月。手术治疗的患者5年生存率72.3%,平均生存期69个月;非手术治疗的5年生存率76.5%,平均生存期47个月（P=0.681）。结论单因素分析显示,胃黏膜相关淋巴组织淋巴瘤预后不良因素包括肿瘤大小（≥10 cm）、浸润深度（侵达浆膜层或浆膜层外）、Ⅲ～Ⅲ期病例、有复发转移,多因素分析显示临床分期为独立预后因素。     

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.     

Clinical analysis of patients with primary and secondary extranodal natural killer/T-cell lymphoma of central nervous system

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.     

原发性卵巢非霍奇金淋巴瘤１０例临床分析

目的　探讨卵巢非霍奇金淋巴瘤（ＮＨＬ）的诊断、治疗及预后。方法　收集本院１９９０年１月至２００８年５月共１０例卵巢ＮＨＬ的手术、化疗及放疗等相关完整的临床资料。结果　１０例均获随访,最长存活５年,最短９个月,中位总生存时间为２６个月。结论　卵巢ＮＨＬ临床上容易误诊,认识其临床特征,尽早采取综合治疗,可以延长患者的生存期。     

Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL)

High Ki-67 is strongly associated with the risk of CNS relapse in patients with mantle cell lymphoma. Two-year incidence of CNS relapse in patients with Ki-67 ≥ 30 exceeds 25%. The incidence was not decreased by rituximab, high-dose cytarabine, high-dose methotrexate or consolidative ASCT. Development of new prophylactic strategies for CNS involvement is mandatory in patients with high Ki-67.BackgroundCentral nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach.Patients and methodsA total of 608 patients (median age, 67 years; range 22–92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis.ResultsNone of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2–141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9–19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5–39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4–4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.     

CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group

BackgroundTo describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma.Patients and methodsWe analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) ± etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved.ResultsFifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1–0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%–9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit.ConclusionsIn younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.     

Central nervous system involvement following diagnosis of non-Hodgkin's lymphoma: a risk model.

BACKGROUND: To determine the incidence and risk factors for central nervous system (CNS) relapse in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patient records were registered prospectively in successive patients with NHL admitted to the Norwegian Radium Hospital from 1980 to 1996. A total of 2514 patients had no CNS involvement at diagnosis and were treated according to standard protocols. The incidence and risk factors for CNS progression or relapse were examined retrospectively. RESULTS: In low-grade (L)-NHL, the risk of CNS involvement was low (2.8%). In high-grade (H)-NHL, lymphoblastic and Burkitt's NHL patients had a high risk of CNS recurrence (24.4%) at 5 years, and prophylaxis seemed to reduce this risk. For the other patients with H-NHL, the proportion with CNS involvement at 5 years was 5.2%. Multivariate analysis identified five independent risk factors, each present in >5% of patients: elevated serum lactate dehydrogenase, serum albumin <35 g/l, <60 years of age, retroperitoneal lymph node involvement and involvement of more than one extranodal site. If four or five of these risk factors were present, the risk of CNS recurrence was in excess of 25% at 5 years. CONCLUSIONS: The risk of CNS involvement in this study is comparable with the results from other large series. CNS prophylaxis is not recommended in any subgroup of L-NHL. The risk of CNS involvement among patients with either Burkitt's or lymphoblastic lymphomas is considerable and these patients should therefore receive intensive chemotherapy including systemic and intrathecal methotrexate. Patients with other types of H-NHL should receive adequate CNS prophylaxis if at least four of the five risk factors identified are present.     

AIDS-related non-Hodgkin's lymphoma: the outcome and efficacy of radiation therapy

The records of all 16 patients with AIDS-related lymphoma treated with radiation therapy at our institutions were reviewed. All patients were male with a median age of 32 years, and all but one had biopsy proven high-grade NHL. Eleven had lymphoma involving the central nervous system and five had lymphoma involving other sites. Seven of the 11 patients with CNS involvement had primary CNS lymphoma. All patients were treated with megavoltage X rays to doses ranging from 1050 cGy in 1 1/2 weeks to 5037 cGy in 6 weeks. Of those patients with CNS lymphoma, only one responded completely and four responded partially to irradiation. All patients died within a range of 0.2 to 5.3 months (median survival = 2.2 months) from starting radiation therapy. In contrast, 3 of 5 patients (60%) with NHL outside the CNS responded completely and 1 responded partially to involved-field irradiation. These patients survived a median of 12.6 months with one achieving long-term lymphoma-free survival at 40 months. This long-term survivor presented with Stage IE lymphoma as his only manifestation of AIDS. We conclude that AIDS-related lymphomas respond less favorably to radiation therapy than lymphomas in non-immunosuppressed patients. Furthermore, CNS lymphomatous involvement is an ominous occurrence in the AIDS patient. In our experience, cranial irradiation failed to provide significant palliation or survival prolongation in this group of patients. Instead, long-term survival is possible in AIDS patients with limited NHL outside the CNS, and it is in these patients that combination chemotherapy plus involved-field radiation therapy may play a curative role.