基于GELOX方案诱导化疗的Ⅰ—Ⅱ期结外鼻型K/T细胞淋巴瘤根治性放疗的预后分析

目的 探讨早期结外鼻型NK/T细胞淋巴瘤(ENKTL)接受GELOX (吉西他滨、奥沙利铂、左旋门冬酰胺酶)方案化疗和放疗疗效及影响因素。方法 回顾分析2007—2013年间收治的74例Ⅰ_E—Ⅱ_E期ENKTL患者,根据化疗方案及有无放疗分为3个组,A组47例为首选GELOX化疗后根治性放疗,B组10例为其他方案化疗改用GELOX挽救后放疗,C组17例为接受GELOX方案化疗后未放疗。全组化疗中位3周期,放疗中位剂量54.6 Gy分20~30次。结果 全组化疗后CR率33.8%(其中放疗后为90%),2年OS和PFS分别为88%和79%。A+C组的疗后CR率、2年OS和PFS分别为73%、92%和84%。A组的2年OS和PFS (96%和84%)均高于B组(50%和45%)和C组(47%和40%,P均<0.05)。单因素分析显示疗前LDH水平升高和化疗后无缓解是OS和PFS的不良预后因素,局部广泛侵犯也是OS的不良预后因素;多因素分析显示化疗后无缓解是OS及PFS的不良预后因素。结论 早期ENKTL患者接受GELOX诱导化疗结合根治性放疗可获得良好疗效,但该方案用于单纯化疗和挽救化疗的疗效仍不理想。     

疗前血清Hb水平在早期结外鼻型NK/T细胞淋巴瘤中的预后价值

目的 探讨治疗前血清Hb水平对早期结外鼻型NK/T细胞淋巴瘤预后的影响。 方法 回顾分析2000—2015年间收治的 175例Ⅰ、Ⅱ期结外鼻型NK/T细胞淋巴瘤。纳入标准为原发病灶位于上消化呼吸道,不合并其他恶性疾病,治疗及随访记录完整病例纳入分析。接受单纯化疗 67例、单纯放疗 8例、放化疗 100例。Kaplan-Meier法计算生存率,Logrank法单因素分析,Cox模型多因素分析。 结果 175例患者的变量单因素分析显示疗前血清Hb水平(≥120 g/L)、LDH水平(正常)、ECOG评分(0~1)、Ann Arbor分期(Ⅰ_{E)、接受放疗显著提高PFS及OS (P=0.000~0.046)。多因素分析显示血清Hb水平、LDH水平、ECOG评分、Ann Arbor分期是患者PFS、OS影响因素(P=0.000~0.040)。 结论 疗前Hb≥120 g/L者预后好于<120 g/L者。}     

二例食管鼻型NK/T细胞淋巴瘤临床病理观察

结外鼻型NK/T细胞淋巴瘤是一种较少见的非霍奇金恶性淋巴瘤,其发病通常和EB病毒感染有关.该病早期临床表现不典型,以坏死性病变为主,具有高度侵袭性,预后较差.我们报道2例罕见的、原发于食管的鼻型NK/T细胞淋巴瘤,并探讨其临床病理特征.     

西南地区鼻和鼻型NK/T细胞淋巴瘤的临床病理特征及预后分析

目的分析西南地区鼻和鼻型NK/T细胞淋巴瘤的临床病理特征及影响预后的因素.方法分析120例鼻和鼻型NK/T细胞淋巴瘤的病理形态及免疫表型、临床特点、治疗和生存情况.结果120例患者总的5年生存率为54.1%.大型瘤细胞生存率较中小型瘤细胞低(P＜0.01),病变中有坏死及血管浸润者生存率明显低于对照组(P＜0.05),而瘤细胞分布及患病年龄与预后关系不大,临床Ⅰ～Ⅱ期与Ⅲ～Ⅳ期两组病例生存率差异有显著性(P＜0.01),累及多个部位、伴有穿孔及全身症状者生存率低于对照组(P＜0.05).综合治疗疗效优于单一治疗及未治疗组(P＜0.01),单一治疗近期疗效好,而远期疗效与未治疗组差异无显著性(P＞0.05).Cox Regression分析结果亦表明瘤细胞大小、分期及治疗方法与预后密切相关.结论瘤细胞大小、坏死、血管浸润、穿孔、B症状、分期、病变范围和治疗方法与鼻和鼻型NK/T细胞淋巴瘤的预后相关,其中瘤细胞大小、分期和治疗方法是其主要的预后因素.     

Clinical study of l‐asparaginase in the treatment of extranodal NK/T‐cell lymphoma,nasal type

Extranodal natural killer/T‐cell lymphoma, nasal type, (ENKTL) is a rare distinct entity of non‐Hodgkin lymphoma. It is prevalent in Asia and Latin America but rare in North America and Europe. ENKTL represents an aggressive clinical course and a poor prognosis especially for advanced disease. There is no standard chemotherapeutic regimen for ENKTL. Recently, the efficacy of l ‐asparaginase in ENKTL has been confirmed. A series of l ‐asparaginase‐containing chemotherapeutic regimens have been studied in clinical trials and have significantly improved the efficacy and prognosis for patients with ENKTL. This review will focus on pharmacology of l ‐asparaginase, the efficacy of a series of l ‐asparaginase‐containing regimens in the treatment of ENKTL and future clinical study directions of l ‐asparaginase‐containing regimens in ENKTL. Copyright © 2015 John Wiley & Sons, Ltd.     

原发肿瘤负荷对结外鼻型NK/T细胞淋巴瘤预后影响

目的 结外鼻型NK/T细胞淋巴瘤尚缺乏有效临床预后和治疗决策因子。本研究旨在定义原发肿瘤负荷(PTB)的临床特征和预后作用。方法 共回顾性收录10家医院1383例病例,其中Ⅰ期947例(68.5%),Ⅱ期326例(23.6%),Ⅲ—Ⅳ期110例(8.0%)。751例患者(54.3%)具有高PTB (H-PTB)特征。Kaplan-Meier法计算生存率Logrank检验,Cox模型多因素分析。结果 H-PTB与疾病侵袭性高、B症状、进展期、区域淋巴结受累、乳酸脱氢酶升高及一般状况差相关。H-PTB组5年OS、PFS更差,分别为50.2%、41.8%,对比低P3TB (L-PTB)分别为72.1%、62.5%(P=0.000、0.000)。多因素分析PTB是OS (HR=1.851)和PFS (HR=1.755)的独立预后因素。H-PTB在局限期患者中,与局部区域控制降低有关,5年局部区域控制率为71.6%,对比L-PTB组为84.3%(P=0.000)。结论 NKTCL中,H-PTB与多个不良临床特征相关,是生存和LC的不良预后因素。H-PTB可作为疾病风险分层和治疗调整的可靠指标。     

Clinical significance of circulating exosomal PD-L1 and soluble PD-L1 in extranodal NK/T-cell lymphoma,nasal-type

Exosomal PD-L1 (exoPD-L1) is reported to be associated with immunosuppression in various cancers. However, its clinical value in extranodal NK/T cell lymphoma (ENKTL) has not been defined yet. We retrospectively evaluated the prognostic value of pretreatment circulating soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) in ENKTL patients treated with VIPD-containing chemotherapy. A total of 107 ENKTL patients, including 101 early stage and 6 advanced stage patients were enrolled in our study. ExoPD-L1 and sPD-L1 in the blood were measured by single molecule array (Simoa) and enzyme-linked immunosorbent assay (ELISA), respectively. Compared with the healthy individuals (n=16), the patients with ENKTL (n=107) exhibited significantly elevated exoPD-L1 and sPD-L1 levels in the blood. High pretreatment plasma exoPD-L1 concentration was associated with higher SUVmax level and recurrence rate. Similarly, high sPD-L1 group was also associated with some adverse clinical parameters, including advanced stage, elevated LDH levels, B symptoms, high IPI score and PINK score. The 5-year progression-free survival (PFS) rate and overall survival (OS) rates were 65.2% and 85.7% for the whole cohort, respectively. Patients with a low pretreatment exoPD-L1 level (simoa signal < 1.2) had 5-year OS and PFS rates of 88.1% and 86.1%, respectively, compared with 56.0%. (P=0.012) and 35.7% (P=0.007) in patients with high exoPD-L1 level (simoa signal > 1.2). The 5-year OS and PFS rates for patients with low sPD-L1 group (< 219 pg/mL) was significantly higher than high sPD-L1 group (≥ 219 pg/mL) (OS, 91.3% vs. 55.5%, P < 0.001; PFS, 68.9% vs. 34.6%, P=0.003). However, no correlation was found between circulating exoPD-L1 and sPD-L1 levels. This is the first study to measure plasma exoPD-L1 level on the Quanterix Simoa platform. Our results proved that circulating exoPD-L1 and sPD-L1 levels were significantly elevated in ENKTL and might be potential biomarkers for predicting the survival outcomes of ENKTL patients.     

早期结外鼻型NK/T细胞淋巴瘤疗后远处淋巴结转移的临床特征

目的 分析 Ⅰ_E~Ⅱ_E期原发上呼吸消化道NK/T细胞淋巴瘤(UADT-NKTCL)经治疗后远处淋巴结转移率及危险因素。方法 1979—2012年共收治 468例Ⅰ_E~Ⅱ_E期UADT-NKTCL患者,其中 170例接受单纯放疗、19例单纯化疗、278例综合治疗、1例抗炎治疗。采用Kaplan-Meier法计算远处淋巴结转移率。结果 中位随访35个月,32例出现远处淋巴结转移,绝对转移率为6.8%(32/468),占总失败病例数的19.8%(32/162),2年远处淋巴结累积转移率为6.4%。71.9%(23/32)合并远处器官转移。最常见转移部位是腹腔淋巴结。单因素分析显示肿瘤原发于鼻腔外上呼吸消化道、Ⅱ_E期、首程治疗疗效未达CR者是远处淋巴结转移的高危因素。多因素分析显示 Ⅱ_E期和首程治疗疗效未达CR是远期复发的独立危险因素,危险度分别为2.82(1.37~5.82,P=0.005)和3.01(1.16~7.78,P=0.023)。Ⅱ_E期综合治疗组的远处淋巴结转移率显著低于单纯放疗组、单纯化疗组,2年远处淋巴结累积转移率分别为12.5%、35.1%、50.0%(P=0.011)。结论 早期UADT-NKTCL治疗后远处淋巴结转移率较低,但对于 Ⅱ_E期和首程疗效未达CR者转移率仍较高。Ⅱ_E期患者建议采用综合治疗以降低远处淋巴结转移率。     

鼻腔NK/T细胞淋巴瘤的预后因素分析

目的探讨鼻腔NK／T细胞淋巴瘤患者预后的影响因素。方法收集61例鼻腔NK／T细胞淋巴瘤患者的临床病理资料,并进行随访。其中30例可取得病理组织标本,用免疫组化方法检测survivin、CD44、nm23、p53、Ki-67、多药耐药基因（MDR-1）和CD95。鼻腔NK／T细胞淋巴瘤患者预后的影响因素采用单因素分析和Cox比例风险模型多因素分析。结果单因素分析显示,一般状况（PS）评分、乳酸脱氢酶（LDH）、Ann Arbor分期、首次治疗的疗效、CD56、Ki-67、CD95与鼻腔NK／T细胞淋巴瘤疾病进展时间（TTP）有关,PS评分、B症状、LDH、首次治疗的疗效、Ki-67、CD95与患者的生存期有关。多因素分析显示,PS评分、Ann Arbor分期、疗效为TTP的独立影响因素,PS评分、疗效为生存期的独立影响因素。结论PS评分、Ann Arbor分期、首次治疗的疗效为TTP的独立影响因素,PS评分、首次治疗的疗效为生存期的独立影响因素。Ki-67高表达可能对预后有不良影响,而CD95高表达则可能有利于患者的预后。     

Primary nasal lymphoma,NK/T‐cell type: Report of two cases with similar presentation but different outcome

Two cases of natural killer (NK)/T‐cell primary nasal lymphoma with similar clinical presentations are reported, for comparison and contrast, to highlight the clinical issues and challenges posed by this unusual disease, its aggressiveness being matched only by its rarity. Presenting as a lesion in the nasal cavity with histological features of malignant lymphoma, primary nasal lymphoma is an uncommon extranodal lymphoma, which poses problems in both diagnosis and management. In people of oriental descent, the common cell subtype is NK/T‐cell. Although it is generally thought that combination treatment with chemotherapy and radiation is the best management for early stage non‐Hodgkin's lymphoma (NHL), there is still debate as to whether combined therapy is optimal treatment for this particular subtype of NHL, given that it responds less well to conventional chemotherapy. Herein we report two patients to illustrate these controversies.     

Life-style and environmental factors in the development of nasal NK/T-cell lymphoma: a case-control study in East Asia

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.     

早期原发鼻腔与韦氏环NK/T细胞淋巴瘤临床特征和预后比较

目的 探讨Ⅰ_E~Ⅱ_E期原发鼻腔与原发韦氏环NK/T细胞淋巴瘤在临床特征和预后等方面的差别。方法 回顾分析1991-2011年本院初治的273例患者,其中Ⅰ_E期184例,Ⅱ_E期89例。原发鼻腔(NC-NKTL)209例和原发韦氏环(WR-NKTL)64例。258例(94.5%)患者先接受化疗,多数患者接受CHOP或类似方案化疗,放疗中位剂量为54 Gy。结果 与NC-NKTL相比,WR-NKTL中Ⅱ_E期和有B症状者显著增多。两组治疗后有效率相近(88.7%和87.9%,P=0.869)。随访率96.3%,随访时间满5年者196例。5年总生存率(OS)和无进展生存率(PFS)分别为52.6%和41.4%,其中NC-NKTL的5年OS有高于WR-NKTL的趋势(57.0%∶39.0%,P=0.062),而5年PFS则高于WR-NKTL的(46.7%∶25.8%,P=0.019)。结论 早期原发韦氏环NK/T细胞淋巴瘤较原发鼻腔病变更易发生全身症状和颈部淋巴结转移,预后较差,临床上考虑提早放疗和颈部淋巴结预防照射。     

Treatment outcome of angiocentric T-cell and NK/T-cell lymphoma, nasal type: radiotherapy versus chemoradiotherapy

OBJECTIVE: The purpose of this study was to evaluate the treatment outcome of angiocentric T-cell and natural killer (NK)/T-cell lymphoma, nasal type. METHODS: Between February 1989 and March 2001, 53 patients with newly diagnosed angiocentric T-cell and NK/T-cell lymphoma, nasal type involving the head and neck, were treated with radiation therapy (RT). There were 37 males and 16 females. The median age of the patients was 45 years (range 19-73). Twenty of them were treated with chemoradiotherapy (CRT), while 33 with treated with RT alone. The median follow-up period was 74 months (range 6-173). RESULTS: The 5-year overall survival rate of all patients was 69%. CRT appeared to be inferior to RT alone in terms of 5-year overall survival, though the difference was not statistically significant (59 versus 76%, P = 0.27). CONCLUSIONS: There was no difference in survival between RT and CRT in angiocentric T-cell and NK/T-cell lymphoma, nasal type.     

结外鼻型NK/T细胞淋巴瘤27例临床分析

 目的　分析结外鼻型NK／T细胞淋巴瘤（ENKL）的临床特征、不同治疗方法的疗效及影响预后的因素。方法　回顾性分析27例ENKL患者,予单纯放疗3例,单纯化疗9例,其余15例采用放化疗联合治疗,其中3例患者行自体造血干细胞移植（auto-HSCT）。对B组症状、乳酸脱氢酶（LDH）、一般状况评分、国际预后指数评分、Ann Arbor分期、治疗模式和近期疗效进行单因素分析。单因素分析采用 Kaplan-Meier法。结果　全组平均生存时间为32（2～42）个月。1、2、3年的总体生存（OS）率分别为79.5 %、71.6 %、53.7 %。早期（Ⅰ期+Ⅱ期）及晚期（Ⅲ期+Ⅳ期）患者2年生存率分别为83.3 %、62.3 %（P＝0.368）,早期患者单纯放疗或化疗4例均获总有效（OR）（CR+PR）,化疗联合放疗10例,OR 9例。晚期患者单纯化疗8例,OR 2例;化疗联合放疗5例,OR 2例。单因素分析显示,年龄及近期疗效是影响生存率的主要因素（P＜0.05）。结论　对于ENKL早期患者,放疗或化疗可取得较好的疗效,放化疗联合治疗及auto-HSCT是治疗晚期ENKL的重要方法。年龄及近期疗效可作为判断ENKL预后的参考因素。     

结外NK/T细胞淋巴瘤鼻型25例预后因素探讨

结外NK／T细胞淋巴瘤鼻型近年来发病率有上升趋势,我们以1999年到2003年于我院住院的25例结外NK／T细胞淋巴瘤鼻型患者为研究对象,就其预后因素进行探讨。     

NK／T细胞淋巴瘤治疗和预后研究进展

NK／T细胞淋巴瘤发病率低,占恶性淋巴瘤2％-10％,其临床病理特征和预后仍不明确,本文就2001年至2009年关于NK／T细胞淋巴瘤临床病理特征、治疗策略和预后因素方面的研究进展作一综述。     

门冬酰胺酶联合GDP方案治疗结外NK/T细胞淋巴瘤的临床疗效观察

  目的   观察左旋门冬酰胺酶（L-asparaginase,L-ASP）联合GDP方案治疗结外NK/T细胞淋巴瘤[extranodal natural killer（NK）/T-cell lymphoma,ENKL]的临床疗效及不良反应。   方法   分析2012年1月至2014年1月间郑州大学附属肿瘤医院收治的初治结外鼻腔NK/T细胞淋巴瘤39例,采用L-GDP方案治疗,具体剂量为左旋门冬酰胺酶6 000/m2,qod×8,d1开始;吉西他滨1 000 mg/m2,d1,8;顺铂90 mg/m2,d1;地塞米松10 mg,d1~4,每21 d为1个周期,完成所有疗程后评价疗效,每周期评价不良反应发生情况,化疗后根据分期选择是否联合放疗或自体移植,观察疗效及不良反应。   结果   39例患者接受中位6个周期L-GDP方案化疗,完全缓解（complete response,CR）为24例,部分缓解（partial response,PR）为7例,疾病稳定（stable disease,SD）为6例,疾病进展（progressive disease,PD）为2例,总有效率（RR=CR+PR）为79.5%（31/39）,全组患者2年无进展生存期（progression-free survival,PFS）为71.8%（28/39）,总生存期（overall survival,OS）为87.2%（34/39）。主要不良反应为胃肠道反应和骨髓抑制及轻度凝血功能异常,25例（64.1%）患者出现恶心呕吐,均能耐受。Ⅲ、Ⅳ度白细胞减少和血小板减少发生率为15.4%（6/39）,82.1%（32/39）的患者出现凝血酶原时间（prothrombin time,PT）、活化部分凝血酶原时间（activated partial prothrombin time,APPT）轻度延长,可自行恢复。未有因严重不良反应而中断治疗者。   结论   L-GDP方案是鼻腔NK/T细胞淋巴瘤安全有效的治疗方案。      

鼻外NK/T细胞淋巴瘤21例临床特征及预后分析

目的 探讨鼻外NK/T细胞淋巴瘤的临床特征与预后.方法 对21例鼻外NK/T细胞淋巴瘤的病例资料进行回顾性分析,并复习相关文献.结果 患者以晚期、有B症状、体能状态（ECOG评分）2～4分、国际预后指数（IPI）3～5分和乳酸脱氢酶（LDH）升高者为多,除1例放弃治疗外,20例患者中,完全缓解5例,部分缓解1例,总生存率为30.0％.早期患者疗效较好,2例晚期合并噬血细胞综合征和弥散性血管内凝血的患者预后最差.结论 鼻外NK/T细胞淋巴瘤患者的预后较差,临床分期、ECOG、IPI和LDH是影响预后的主要因素.     

NK/T细胞淋巴瘤治疗和预后研究进展

NK/T细胞淋巴瘤发病率低,占恶性淋巴瘤2%-10%,其临床病理特征和预后仍不明确,本文就2001年至2009年关于NK/T细胞淋巴瘤临床病理特征、治疗策略和预后因素方面的研究进展作一综述。