系统性间变性大细胞淋巴瘤骨髓累及的临床病理学研究

目的 探讨系统性间变性大细胞淋巴瘤(S-ALCL)骨髓累及的临床病理学特点、免疫学表型及临床生物学行为.方法 回顾性分析34例S-ALCL病例资料,进行骨髓活检(19例)或涂片(15例).其中ALK(+)24例,ALK(-)10例.HE染色、免疫组织化学染色观察病理形态及免疫表型,原位杂交法检测EB病毒.结果 6例(17.6%)S-ALCL存在骨髓累及,均经骨髓活检标本确定,15例患者骨髓涂片中均未见肿瘤累及.ALK(+)ALCL和ALK(-)ALCL骨髓累及的发生率分别为16.7%(4/24)和20.0%(2/10),差异无统计学意义(P=0.3555).与无骨髓累及病例比较,骨髓累及病例的年龄、性别分布差异无统计学意义(P值分别为0.8089和0.3085).骨髓累及者肿瘤细胞以间质性分布为主[83.3%(5/6)].生存分析统计提示伴有骨髓累及的患者预后明显差于无骨髓累及者(P=0.0407).结论 S-ALCL骨髓累及发生率低,与患者的发病年龄、性别及ALK蛋白的表达无相关性.伴有骨髓累及的S-ALCL患者临床预后差,骨髓活检在判断S-ALCL预后中有重要意义.     

原发系统性间变性大细胞淋巴瘤临床病理特征及免疫表型分析

目的 分析原发系统性间变性大细胞淋巴瘤( ALCL)的临床病理特征和免疫组织化学特点,提高诊治水平。方法选取22例ALCL患者,均进行分期、国际预后指数(IPI)、乳酸脱氢酶(LDH)检测,应用免疫组织化学SP法检测间变性淋巴瘤激酶(ALK)、Ki-67、Caspase-3、CD30、EMA、Granzyme B等,回顾性分析患者临床、病理形态学资料、免疫表型及生物学特性,并进行预后分析。结果22例均为原发系统性ALCL,ALK+ 15例(68.2％),ALK-7例(31.8％);AILK+患者发病年龄、Ki-67增殖指数较ALK-患者低,Caspase-3表达率高,差异有统计学意义(x2 =4.618,P= 0.032);15例ALK+ALCL均表达CD30和EMA。ALCL中ALK的表达与Ki-67、Caspase-3的表达呈负相关(r= -0.581,P= 0.006;r=0.458,P=0.032)。ALK+病例较ALK-病例GranzymeB(x2=0.11,P=0.74)、TIA-1( x2= 0.01,P=0.92)的表达率高,但差异无统计学意义(P＞0.05)。有效率为54.5％(12/22),其中完全缓解率为18.2％(4/22);全组中位生存期12个月,1年生存率为59.1％( 13/22),2年生存率为50.0％(11/22)。Ann Arbor分期、LDH及IPI与疾病预后相关。结论ALK+较ALK-ALCL患者核增殖低,恶性程度低,临床特征和免疫表型具有一定的特征性;ALK、Ki-67、Caspase-3、分期、血清LDH及IPI对预测ALCL患者的生存和指导治疗有帮助。     

中枢神经系统血管内ALK阳性间变性大细胞淋巴瘤一例并文献复习

目的 报道1例血管内间变性大细胞淋巴瘤激酶阳性(ALK+)间变性大细胞淋巴瘤(ALCL),提高对血管内淋巴瘤(IVL)的认识.方法 分析1例中枢神经系统血管内ALK+ALCL的临床资料、组织病理学特点和免疫表型,并结合文献进行复习.结果 患者女性,41岁.CT示右侧顶枕叶不规则低密度灶,增强扫描壁结节及边缘明显强化;磁共振(MRI)示右顶枕叶斑片状不规则异常信号影,累及右侧胼胝体压部,增强扫描呈斑片状不规则强化.血常规示单核细胞比例增高,红细胞压积减少.光学显微镜下观察:脑实质小血管管腔内多量明显异型性大单核细胞,肿瘤细胞胞质丰富嗜伊红,核圆形或不规则,可见马蹄形或肾形核,核仁清楚.免疫组织化学:肿瘤细胞LCA(+)、CD,(+)、ALK-1(+)、EMA(+)、粒酶B(+)、CD20(-)、CD79a(-)、CD30(-)、CD56(-)、GFAP(-)、AE1/AE3(-)、HMB45(-),血管内皮细胞CD31(+)、CD34(+).患者手术后8个月死亡,未行放化疗.结论 血管内ALK+ ALCL是IVL的一种罕见亚型,细胞形态特点及免疫表型类似于淋巴结或结外ALCL,临床症状无特异性,预后差,确诊主要依靠组织病理学检查.     

原发结内外周T细胞淋巴瘤19例临床特征及预后分析

目的 分析原发结内外周T细胞淋巴瘤(PTCL)的临床特点、治疗和预后.方法 回顾性分析19例原发结内PTCL患者的临床资料、治疗反应以及预后因素.结果 19例患者中位发病年龄54岁,男女比例2.17∶1,其中94.7%(18/19)为Ⅲ～Ⅳ期,84.2%(16/19)有B症状,84.2%(16/19)有结外器官受累,57.9%(11/19)有骨髓浸润.化疗完全缓解(CR)率36.8%(7/19),2年总生存(OS)率47.4%,2年无进展生存(PFS)率25%.预后分析显示,结外侵犯数量(EN)≥2个、美国东部肿瘤协作组(ECOG)体能状态评分≥2分、国际预后指数(IPI)评分＞2分以及β2-微球蛋白(βrMG)升高为不良预后因素.结论 原发结内PTCL是一类高度侵袭的异质性T细胞淋巴瘤,化疗效果差,多项因素提示不良预后.     

P53突变蛋白表达对弥漫大B细胞淋巴瘤预后的预测作用

目的 探讨p53突变蛋白表达对弥漫大B细胞淋巴瘤(DLBCL)预后的预测作用,指导个体化治疗.方法 随机选择初治DLBCL患者62例,应用免疫组织化学方法检测p53突变蛋白和CD10、bcl_6、MUM1的表达,分析p53突变蛋白表达与患者临床特征、分子分型以及预后的关系.结果 48.4%(30/62)的患者表达p53突变蛋白.p53突变蛋白表达与初始治疗反应有关(x2=20.365,P=0.040),阳性组的完全缓解率为33.3%(10/30),阴性组为59.4%(19/21);与分子分型有关(x2=31.023,P=0.021),阳性组非生发中心型比例显著高于阴性组,分别为83.3%和56.2%;与其他临床特征无关.多因素生存分析显示p53突变蛋白表达是独立的预后预测因子,阳性组的无进展生存期和中位生存期均短于阴性组(x2=36.784,P=0.005和x2=35.276,P=0.006).结论 p53突变蛋白表达是DLBCL独立的不良预后因子,能够用来指导个体化治疗.     

鼻腔自然杀伤/T细胞淋巴瘤放射治疗的疗效和影响因素

目的 回顾分析鼻腔自然杀伤(NK)/T细胞淋巴瘤的放射治疗效果,并分析其预后因素.方法 回顾分析9年间接受放射治疗的62例鼻腔NK/T细胞淋巴瘤的临床资料和疗效,单因素分析采用Kaplan-Meier法,多因素分析用COX比例风险模型.结果 全组中位生存时间69.7个月(95%CI为63.0～78.0个月),3、5年总生存率分别为66.1%和46.8%,远处转移导致治疗失败占61.8%.T淋巴细胞CD3升高组和降低组的中位生存时间分别为72.6个月和39.6个月,两组比较差异有统计学意义(x2=4.9309,P=0.0264).多因素分析表明,修正后国际预后指数(IPI)为0～1(x2=7.5266,P=0.0061)、CD3升高(x2=9.0912,P=0.0266)和治疗结束达到CR(x2=9.0912,P=0.0106)是影响鼻腔NK/T细胞淋巴瘤放疗总生存的有利预后因素.结论 放射治疗鼻腔NK/T细胞淋巴瘤疗效肯定,但远处转移治疗失败率高,全身治疗仍具有重要地位;修正后IPI为0～1、CD3升高、治疗结束达到CR是影响鼻腔NK/T细胞淋巴瘤放疗总生存的有利预后因素.     

原发性纵隔大B细胞淋巴瘤研究进展

原发性纵隔大B细胞淋巴瘤(PMBCL)是弥漫大B细胞淋巴瘤(DLBCL)的一种特殊类型,具有独特的临床表现及病理学、分子生物学特征.目前尚无标准的治疗方案,回顾性分析表明第三代的化疗方案优于CHOP方案,利妥昔单抗的应用缓解了这种差异,是否需要接受联合放疗尚无定论.未来将脱氧葡萄糖-正电子发射计算机断层显像(FDG-PET)用于PMBCL的疗效评估,如果能提供可靠的预后信息,就可以减轻治疗强度.     

改良VDLP方案治疗难治复发NK/T细胞淋巴瘤13例

目的 观察以左旋门冬酰胺酶为主的改良VDLP方案治疗难治复发NK/T细胞淋巴瘤的疗效及不良反应.方法 13例难治复发NK/T细胞淋巴瘤患者,治疗方案均选用改良VDLP方案:长春新碱1.4 mg·m-2·d-1,第1天;左旋门冬酰胺酶6000 U·m-2·d-1,第1天至第7天;多柔比星或表柔比星30 mg·m-2·d-1,第1天至第3天,泼尼松40mg·m-2·d-1,第1天至第7天.21 d为1个周期,所有患者均接受2～6个周期,中位3.5个周期,病灶局限的患者,化疗后加用侵犯野放疗.结果 13例患者中,总有效率61.5%(8例),完全缓解46.1%(6例),部分缓解7.6%(1例),病情稳定7.6%(1例),进展38.5%(5例).中位随访27(13～51)个月,全组预期3年生存率为63.4%;主要不良反应为骨髓抑制,Ⅲ～Ⅳ度粒细胞减少占30.4%,无治疗相关死亡.结论 以左旋门冬酰胺酶为主的VDLP方案治疗复发难治的NK/T细胞淋巴瘤患者疗效好,不良反应小且耐受性好,值得临床推荐使用.     

儿童侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点

目的 分析总结中国儿童各类型侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点,为其诊断的标准化提供依据.方法 收集97例儿童侵袭性成熟B细胞淋巴瘤石蜡包埋组织标本,包括伯基特淋巴瘤(BL)81例、弥漫大B细胞淋巴瘤(DLBCL)8例、介于BL和DLBCL间的不能分类的B细胞淋巴瘤(BL/DLBCL)8例,利用免疫组织化学技术和间期荧光原位杂交(FISH)技术检测其免疫表型和分子遗传学特征.结果 BL的bcl-2和MUM1的阳性率分别为3%(2/66)和17%(12/71),DLBCL分别为50%(4/8)和63%(5/8),BL/DLBCL分别为50%(4/8)和63%(5/8).BL、DLBCL和BL/DLBCL的Ki-67平均值分别为(93±4.4)%、(83±14.3)%和(80±11.5)%.BL、DLBCL和BL/DLBCL的c-myc基因易位的比例分别为98%(79/81)、38%(3/8)和50%(4/8).38%(3/8)的DLBCL和25%(2/8)的BL/DLBCL存在bcl-6基因的多拷贝,BL与DLBCL之间、BL与BL/DLBCL之间bcl-2、MUM1和Ki-67平均值的差异及c-myc基因易位和bcl-6基因多拷贝的差异均有统计学意义(均P＜0.05).结论 儿童侵袭性成熟B细胞淋巴瘤的诊断和分型需要综合分析形态学、免疫表型和分子遗传学特征.儿童BL/DLBCL可能是DLBCL的一个亚型.CD10+、bcl-6+、bcl-2-、Ki-67＞90%、伴有IGH/c-myc重排、不伴有bcl-2和bcl-6重排时,支持BL的诊断;bcl-2+、Ki-67为50%～90%,同时伴有bcl-6基因的多拷贝时,支持DLBCL或BL/DLBCL的诊断.     

鼻型自然杀伤-T细胞淋巴瘤31例临床分析

目的 分析结外鼻型自然杀伤(NK)-T细胞淋巴瘤的临床特点及治疗方案,提高对鼻型NK-T细胞淋巴瘤的认识.方法 对经病理证实的鼻型NK-T细胞淋巴瘤31例的临床资料进行回顾性的分析结果31例患者中,EB病毒(EBV)感染24例(77.42%).近期疗效结果显示,放疗、化疗、放疗+化疗差异无统计学意义(x2=3.61,P＞0.05).随访截至2010年10月,3l例患者中死亡24例,7例生存,其中4例无瘤生存.19例死于肿瘤复发或进展.全组中位生存时间为32个月.患者5年生存情况与临床分期、区域淋巴结受累、B症状、乳酸脱氢酶(LDH)水平、局部肿瘤浸润、EBV感染、早期治疗有 关(x2值分别为8.88、7.25、16.95、6.00、7.23、7.44、7.80,均P＜0.05).结论 放疗、化疗、放疗+化疗治疗鼻型NK-T细胞淋巴瘤疗效差异不大;患者的生存情况与临床分期、区域淋巴结受累、B症状、LDH水平、局部肿瘤浸润、EBV感染、早期治疗等临床特征有关.     

Non-Hodgkin's lymphoma of stage I and II in elderly patients: a retrospective study in comparison with younger patients

Forty-one patients with non-hodgkin's lymphoma at stages I and II who had received radiation therapy were reviewed to analyze the prognosis and prognostic factors, with the main focus on a comparison of elderly (age > 65 years) and younger patients. In terms of clinical and histological characteristics, there were no differences between the elderly and younger patients. The 5-year-survival rate (5YS) in elderly patients was 52.8%, compared with 68.6% for younger patients. In patients treated with irradiation alone, the 5YS was 49.5% in elderly patients and 22.1% in younger patients. Combination treatment consisting of irradiation and chemotherapy improved 5YS markedly to 84.9% in the younger patients, while no apparent improvement was seen in the elderly patients, in whom 5YS was 54.1%. Using Cox's multiregression life table, two prognostic factors, the presence of symptoms and LDH, were extracted and found to have a significant influence upon the survival of the elderly patients. Complete response was 90.2% in the elderly patients, although relapse was seen in 54.1% of the complete responders. Relapse occurred overwhelmingly outside the irradiated regions. Since the prognosis of elderly patients could not be improved with the current chemotherapy regimen, some different regimen must be established to lower the high relapse rate in the area outside the irradiated field.     

Prognostic factors for patients with advanced seminoma treated with platinum-based chemotherapy

Prognostic factors for 3-year progression-free survival (PFS) were defined in 286 patients with advanced seminoma treated with cisplatin-based chemotherapy at 10 European oncology units (no prior treatment: 236; prior radiotherapy: 50). Previously irradiated patients displayed a 69% PFS as compared to 87% in those presenting with advanced seminoma at the time of diagnosis (P = 0.009). In the univariate analysis, the extent and site of disease before chemotherapy and the level of serum LDH (< 2.0 versus > or = 2.0 x upper limit of normal) correlated with PFS in previously non-irradiated patients, but not in patients with prior radiotherapy. The multivariate analysis was, therefore, restricted to previously non-irradiated patients. The presence of non-pulmonary visceral metastases and a serum LDH level of > or = 2 x normal (N) proved to be independent prognostic factors. Based on these variables, two prognostic models were constructed and validated in an external data set of 166 comparable patients. For clinical use, Model 2 is recommended. The good-prognosis group comprises non-irradiated patients with stage II seminoma and any LDH level at presentation, or stage III and IV patients (with lung metastases only) whose serum LDH level is < 2 x N. These patients display a 94% 3-year PFS. The poor prognosis group includes all other patients with a 56% PFS. With this prognostic model, individualisation of the therapeutic approach may be considered in patients with advanced seminoma and a high risk of chemotherapy-related toxicity.     

CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology

The purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level >/=800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.     

Mutational destabilization of the critical interface water cluster in Scapharca dimeric hemoglobin: structural basis for altered allosteric activity

We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54.8% (SD 1.9), 43.1%) (SD 2.7) and 55.6% (SD 2.2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (> 50 x 10(9)/l), circulating blastosis. haemoglobin >12 g/dl, platelet count <100 x 10(9)/l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10+ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH >400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1.1% for gender, 2.0% for age, 3.5% for leucocytosis, and 1.6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL.     

Current guidelines for the management of aggressive non-Hodgkin's lymphoma

The prognosis of aggressive non-Hodgkin's lymphoma (NHL) has improved greatly during recent years with the use of combination chemotherapy. Planning the treatment must take into consideration the patient's age, performance status, histological subtype and disease extent and severity. Recently, a 4-part International Prognostic Index (IPI), based on 5 prognostic factors, has permitted the allocation of patients with NHL in 2 well defined prognostic groups: good prognosis (low and low-intermediate risk) and poor prognosis (intermediate-high and high risk). Conventional chemotherapy with CHOP (a chemotherapeutic regimen consisting of a combination of cyclophosphamide, doxorubicin, vincristine and prednisone) or other equivalent third-generation regimens may be considered the standard treatment for the good prognosis group. In the poor prognosis group the probability of long term survival is less than 40% with conventional chemotherapy. Therefore, an early intensification with high dose therapy following peripheral stem cell transplantation (PSCT) should be considered in the setting of randomised trials. Localised stage disease, defined as stages I-IE and II-IIE without adverse prognostic factors, has a very good prognosis with a long term survival exceeding 80% using brief conventional chemotherapy regimens plus involved field radiotherapy. Refractory or relapsing patients after the drugs of first choice are given who subsequently respond to salvage chemotherapy should be enrolled for a course of high dose consolidation chemotherapy followed by PSCT. Elderly patients without severe organ dysfunction can take advantage from specifically devised chemotherapy regimens, with a response rate similar to that of younger patients. However, despite major advances in the treatment of aggressive NHL, additional clinical trials are required to enable the clinician to define the best therapeutic programmes to treat patients with this disorder.     

Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years

The purpose of this study was to analyse the presenting clinical and laboratory features and the outcome of 72 patients with multiple myeloma (MM) who were younger than 40 years. The records of all Mayo Clinic patients with MM younger than 40 years who were seen between 1 January 1956 and 31 December 1992 were reviewed. Survival was measured from the date when treatment was required to the date of last follow-up or death. The frequency of MM in patients younger than 40 and 30 years in 3278 Mayo Clinic patients was 2.2% and 0.3%, respectively. The main presenting clinical features were bone pain (66%), fatigue (26%), extramedullary plasmacytomas (19%) and bacterial infection (11%). Renal function impairment (creatinine level > or = 177 micromol/l) and hypercalcaemia (serum calcium value > or = 2.75 mmol/l) occurred in 29% and 30% of patients, respectively. Among the 57 patients evaluable for response the objective response rate was 54%. 14/35 patients treated with a single alkylating agent achieved an objective response, whereas 17/22 patients given combination chemotherapy had an objective response (P=0.013). However, this higher response rate did not result in a significantly longer survival. The median survival for the 72 patients was 54 months. Patients with good prognostic features (normal renal function or low beta 2-microglobulin level) had a median survival of 8 years. The actuarial survival at 5 and 10 years after initiation of therapy was 43% and 13%, respectively. In summary, survival in very young patients with myeloma is longer than that observed in series of patients of all ages, especially in those with good prognostic factors.     

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.