HLA单倍相合造血干细胞移植治疗恶性血液病的临床研究

目的 探讨人类白细胞抗原(HLA)单倍相合造血干细胞移植(HSCT)治疗恶性血液病的疗效和主要并发症.方法 对2004年7月至2006年12月第三军医大学附属新桥医院收治的35例恶性血液病患者进行HLA单倍相合亲缘供者HSCT.采用延长、强化联合免疫抑制促进植入、抗胸腺细胞球蛋白(ATG)加强预防移植物抗宿主病(GVHD)、粒细胞集落刺激因子(G-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植方案.结果 所有患者均重建供者造血.18例(51.4%)发生急性GVHD(aGVHD),其中Ⅰ度8例,Ⅱ度5例,Ⅲ度3例,Ⅳ度2例,Ⅱ～Ⅳ度aGVHD累积发生率为28.6%.12例(34.3%)发生慢性CVHD(cGVHD),均为局限性.23例患者存活,总存活率为65.7%,2年无病存活率(DFS)为62.9%.12例患者死亡,7例死于复发,5例死于移植相关合并症,其中肺部感染2例,Ⅳ度GVHD 2例,巨细胞病毒(CMV)感染1例.结论 随着预处理方案、GVHD预防方案及移植物成分的优化,HLA单倍相合造血干细胞移植的疗效明显改善,已成为治疗恶性血液病的重要方法.     

HLA半相合血缘性骨髓移植治疗慢性粒细胞白血病4例

目的:探索半相合未去除T细胞骨髓移植治疗慢性粒细胞白血病的可行性。方法:4例慢性粒细胞白血病患者接受HLA1或2个位点不相合亲缘骨髓移植。用阿糖胞苷、环磷酰胺和全身照射进行预处理,供者应用GCSF250μg/d,连用7d后采髓。移植物抗宿主病(GVHD)预防除用环孢菌素A(CsA)和甲氨蝶呤(MTX)外,在移植前第4天～第1天用抗胸腺细胞球蛋白ATG(兔抗)2.5mg/(kg·d),移植后第7天开始加用霉酚酸酯1.0g/d。结果:患者移植后均获得造血重建,中性粒细胞>0.5×109/L和血小板>20×109/L的中位时间分别是12.5(10～14d)和22d(18～25d)。4例患者发生急性Ⅰ度GVHD,其中1例2个位点不相合者进展为急性肠道和肝脏Ⅳ度GVHD,于+81d合并感染死亡。1例发生迟发性出血性膀胱炎。中位随访时间20个月(5～25个月)。无病存活3例,其中2例存活在1年以上。结论:供者应用GCSF后采髓,多种免疫抑制剂联合应用的HLA不全相合未去除T细胞骨髓移植,在治疗慢性粒细胞白血病过程中,有效地降低了急性重症GVHD发生,提高了无病生存。     

含全身照射预处理方案行HLA不相合非去T造血干细胞移植治疗白血病8例临床分析

目的探讨采用全身照射(TBI)预处理方案行人类白细胞抗原(HLA)配型不相合亲缘供者非去T异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效。方法2002年4月至2007年1月北京大学血液病研究所8例采用TBI预处理方案行HLA不合非去T亲缘供者allo-HSCT的白血病患者,其中急性髓性白血病(AML)3例,急性淋巴细胞性白血病(ALL)4例,慢性粒细胞白血病1例;预处理方案采用TBI加环磷酰胺(CY)方案4例,TBI加氟达拉滨(FLU)方案4例;干细胞来源包括骨髓和外周血造血干细胞移植6例,外周血造血干细胞移植(PBSCT)2例;移植物抗宿主病(GVHD)预防采用经典的环孢素A(CsA) 霉酚酸酯(MMF) 短程甲氨蝶呤(MTX)方案。结果8例供者采集单个核细胞(MNC)中位数为7.39(6.27~12.46)×108/kg,粒细胞植入中位时间11(11~13)d,血小板植入中位时间13(11~21)d。5例发生Ⅰ~Ⅱ度急性GVHD,2例出现慢性广泛性GVHD,无严重急性GVHD或因GVHD死亡病例。中位随访时间9(3~53)个月,除1例复发存活外,其余病例无病存活。结论对于HLA不相合异基因造血干细胞移植,TBI方案是一种比较安全、有效的非去T预处理方案,对于高危和二次移植患者同样有效。     

异基因造血干细胞移植治疗白血病76例临床观察

目的观察不同来源的异基因造血干细胞移植治疗白血病的疗效并探讨主要并发症的处理方案。方法对2001年9月至2007年3月第四军医大学西京医院血液科76例白血病患者行异基因造血干细胞移植治疗,其中慢性粒细胞白血病34例,急性髓性白血病24例,急性淋巴细胞白血病15例,T细胞淋巴瘤/白血病3例。人类白细胞抗原(HLA)全相合的同胞供者57例,1个HLA位点不合同胞供者3例,HLA单倍型半相合同胞供者7例,非血缘供者9例。预处理方案采用改良的马利兰联合环磷酰胺(BUCY)或改良的环磷酰胺联合全身放疗及阿糖胞苷或鬼臼乙叉甙(CyTBI Ara-c/VP-16)方案。采用标准的环孢素A(CsA)联合短期甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD);无关供者移植加用抗人胸腺细胞球蛋白,单倍型半相合移植同时加用CD25单克隆抗体。结果96.1%(73/76)获得植入。24.7%(18/73)出现急性GVHD,32.9%(24/73)出现慢性GVHD;合并重症肝静脉闭塞病2例;并发纯红细胞性再生障碍性贫血5例。随访3~72个月,现存活56.6%(43/76),43.4%(33/76)在移植后1~36个月时死亡,19例死于白血病复发,14例死于移植相关并发症。结论多种来源的异基因造血干细胞移植是治疗白血病的有效方法,于慢性粒细胞白血病慢性期、急性白血病缓解期移植效果较好,移植前处于高危难治状态的病例复发率仍较高。     

3例复发难治性B细胞急性淋巴细胞白血病的治疗及移植物抗宿主病预防

目的 通过对3例复发难治性B细胞急性淋巴细胞白血病(B-ALL)患者的治疗方法及移植治疗后移植物抗宿主病(GVHD)的预防方法分析,总结这类疾病有效治疗方案及预防方案.方法 3例复发难治性B-ALL患者中2例为费城染色体Ph(+),在确定半相合供者后,给予CD19靶向嵌合抗原受体T(CAR-T)细胞桥接治疗,缓解后接受亲缘半相合异基因造血干细胞移植(haplo-HSCT),采用造血干细胞移植方案GIAC进行移植治疗,同时在移植后给予小剂量环磷酰胺(PTCY,14.5 mg/kg体质量)预防GVHD.结果 3例B-ALL患者CAR-T细胞治疗后均获得了完全缓解(CR),其中2例达分子生物学缓解,1例达流式MRD阴性缓解;其中2例患者顺利接受haplo-HSCT,回输后均成功供者细胞造血重建,无严重GVHD,白血病疾病状态稳定.另1例伴有p.T315I突变的Ph(+)-ALL患者,CAR-T细胞治疗后获得短暂分子生物学缓解,但在移植准备过程中再次复发后失去移植机会.结论 CAR-T治疗后序贯亲缘半相合移植治疗复发难治性B-ALL患者效果良好;小剂量PTCY联合GIAC移植方案可以安全有效地预防GVHD的发生;CAR-T细胞治疗后短期再次复发的B-ALL患者目前仍然治疗困难.     

单倍体相合造血干细胞移植在难治高度恶性淋巴瘤中的应用

目的 :探讨应用单倍体相合骨髓移植对难治高度恶性非霍奇金淋巴瘤 (NHL)治疗的可行性。方法 :6例难治高度恶性NHL伴有骨髓浸润患者接受人白细胞抗原 (HLA) 2～ 3个位点不合的单倍体相合移植 ,供者用粒细胞集落刺激因子 (G CSF)促进后采髓 ,急性移植物抗宿主病 (GVHD)预防例 1采用环孢菌素A(CSA)、短程甲氨蝶呤 (MTX)、霉酚酸酯 (MMF)和抗胸腺细胞球蛋白 ,余 5例除上述药物外 ,还加用CD2 5单克隆抗体。结果 :6例移植后均获造血重建 ,粒细胞绝对数 >0 .5× 10 9/L中位天数是 17d ,血小板 >2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。 1例于移植后 2 0d时发生急性Ⅳ度肠道GVHD ,可评价慢性GVHD病例4例 ,均发生慢性GVHD ,其中 1例广泛性慢性GVHD ,口服泼尼松和CSA病情控制。中位随访 2 0 (7～ 4 2 )个月 ,1例重度GVHD于移植后 2个月死亡 ,1例在移植后 4个月并发真菌感染死亡 ,无病存活 4例 ,Karnofshy生存质量评价为 10 0 %。结论 :研究表明单倍体相合未经体外去T细胞骨髓移植对难治高度恶性NHL具有一定治疗价值 ,能够降低急性重症aGVHD发生和减少移植相关死亡。     

HLA配型不合/单倍型造血干细胞移植供者淋巴细胞输注量与急性移植物抗宿主病的关系

急性移植物抗宿主病（aGVHD）是单倍型造血干细胞移植（HSCT）最常见的并发症之一。其发生率和病死率都较高，而且发病机制非常复杂。T细胞起着核心作用，移植物内T细胞过多可导致GVHD，而去除T细胞或T细胞亚群可以预防GVHD，但移植物被排斥和白血病／淋巴瘤的复发率增多。本研究检测59例HLA配型不合／单倍型HSCT供者淋巴细胞及T细胞亚群数，并分析其与受者aGVHD的关系。     

HLA半相合非清髓性造血干细胞与间充质干细胞共移植治疗重症再生障碍性贫血1例

目的:观察HLA半相合非清髓性造血干细胞与间充质干细胞(MSC)共移植治疗重症再生障碍性贫血(SAA)的疗效及安全性。方法:1例24岁男性SAA患者。应用非清髓性预处理方案,进行HLA半相合异基因外周血造血干细胞和MSC共移植。移植rhG-CSF动员的供者外周血单个核细胞9.22×108/kg,CD34 细胞8.56×106/kg,及体外扩增培养的供者骨髓MSC2.12×105/kg。结果:移植后 12d中性粒细胞数>0.5×109/L, 21d WBC4.5×109/L,Hb99g/L,PLT108×109/L。经HLA配型,红细胞亚型和VNTR检测,为供者型完全嵌合体。随访14个月,无急、慢性移植物抗宿主病(GVHD)发生。结论:HLA半相合非清髓性造血干细胞与MSC共移植治疗SAA是安全有效的方法。     

单倍型相合骨髓移植治疗伴髓外侵犯的难治复发变异型急性早幼粒细胞白血病获长期生存1例并文献复习

目的:探讨单倍型相合骨髓移植治疗伴有髓外侵犯的难治性变异型急性早幼粒细胞白血病的疗效。方法:采用母亲供髓的单倍型相合移植治疗1例伴髓外侵犯的难治复发变异型急性早幼粒细胞白血病,预处理方案为CyTBI加Ara-c,GVHD预防采用联合免疫抑制剂和供者应用G-CSF的方法,联合免疫抑制剂包括环胞素A、短程氨甲碟呤、霉酚酸酯、CD 25单抗和抗胸腺细胞球蛋白的应用。结果:移植后+1个月造血重建,植入成功,免疫功能逐渐恢复,定期随访,PML/RARα融合基因持续(-),现已无病生存76个月。结论:单倍型相合骨髓是治愈高危难治复发急性早幼粒白血病的有效措施,为患者提供了长期生存的机会。     

人类白细胞抗原单倍型相合外周血造血干细胞移植治疗血液系统疾病的疗效与安全性

 目的 评价非去T细胞人类白细胞抗原（HLA）单倍型相合外周血造血干细胞移植治疗血液系统疾病的疗效与安全性。方法 回顾性分析2007年7月—2011年12月在解放军总医院行HLA单倍型相合外周血造血干细胞移植的病例资料。结果 49例移植受者中位年龄22（3~59）岁。供受者HLA配型5/10相合15例,6/10相合11例,7/10相合7例,8/10相合5例,9/10相合11例。输注的单个核细胞中位数为10.01(7.05~25.34)×10⁸/kg,CD⁺₃₄细胞中位数为4.51 (2.01~11.47)×10⁶/kg。1例复发难治型白血病患者植入失败。髓系造血重建中位时间为14（10~25）d,血小板重建中位时间为22（10~135）d。移植后中位随访时间347（7~1765）d。移植后100 d急性移植物抗宿主病（aGVHD）累计发生率为(61.6±7.3)%,Ⅱ~Ⅳ度aGVHD 累计发生率为(28.6±6.7)%。2年慢性移植物抗宿主病（cGVHD）累计发生率为(42.6±8.5)%,广泛性cGVHD累计发生率为(22.7±7.6)%。100 d移植相关死亡累计发生率为(14.7±5.1)%,2年移植相关死亡累计发生率为(30.9±8.8)%;移植后2年累计复发率为(25.4±7.0)%。2年累计总生存率和无病生存率分别为(58.1±8.8)%和 (53.9±8.4)%。结论 非去T细胞亲缘HLA单倍型相合外周血造血干细胞移植是一种有效的造血干细胞移植方式。     

Thoracic radiotherapy in patients with lymphoma and restenosis after coronary stent placement.

OBJECTIVES: The aim of this study was to assess the incidence of restenosis after coronary stenting in patients with lymphoma treated with thoracic radiation. BACKGROUND: Patients with Hodgkin lymphoma treated with thoracic radiation have an increased incidence of coronary artery disease (CAD). The incidence of restenosis after percutaneous coronary interventions is completely unknown. METHODS: This study included 12,626 consecutive patients with CAD treated with coronary stenting during a 10-year period. Within this cohort, three subgroups of patients were assessed: patients with lymphoma and previous thoracic radiation (15 patients), patients with lymphoma without thoracic radiation (7 patients) and patients without lymphoma or previous thoracic radiation (control group; 12,604 patients). Coronary stenting was performed after a median [25th; 75th percentiles] of 8 years [4; 17] after thoracic radiation. The primary end point of the study was restenosis at 6-month coronary angiography. RESULTS: Six-month coronary angiography was performed in 14 patients (93%) in the group with lymphoma and radiation, 6 patients (86%) in the group with lymphoma without radiation and 10,032 patients (80%) in the control group (P = 0.38). Angiographic restenosis was found in 12 patients (85.7%) in the group with lymphoma and radiation, 1 patient (16.7%) in the group with lymphoma without radiation and 2,555 patients (25.5%) in the control group (P < 0.001). Multiple logistic regression identified thoracic radiation as an independent predictor of coronary restenosis (odds ratio 21.7, 95% confidence interval, 4.7-100.9, P < 0.001). CONCLUSIONS: Patients with lymphoma treated with thoracic radiation have an increased risk of restenosis after coronary artery stenting.     

原发性肠淋巴瘤与克罗恩病的鉴别诊断

背景：原发性肠淋巴瘤的发病率较低，临床表现缺乏特异性，易误诊为其他胃肠道疾病，特别是与克罗恩病（CD）的鉴别诊断较困难。目的：通过分析原发性肠淋巴瘤和CD患者的临床资料，提高原发性肠淋巴瘤与CD的鉴别诊断水平。方法：回顾性分析原发性肠淋巴瘤和CD患者的临床特点、内镜表现和病理检查结果。结果：原发性肠淋巴瘤患者的平均年龄为50岁，CD为35岁。5例（12.2％）CD发生肛周病变，4例（9.8％）内瘘，3例（7.3％）有肠外表现，但仅1例（5.9％）原发性肠淋巴瘤曾有肛瘘。内镜下原发性肠淋巴瘤以回盲部受累多见（41.7％），CD以小肠和结肠均受累多见（48，8％）；原发性肠淋巴瘤以肿块型较多见（41.7％），CD则主要表现为溃疡和铺路石样改变，其中18例伴肠腔狭窄，4例瘘管形成。B细胞性原发性肠淋巴瘤13例，T细胞性4例。12例CD表现为非干酪样坏死性肉芽肿。结论：临床上原发性肠淋巴瘤与CD的鉴别诊断较困难，需综合各种检查手段，特别是内镜检查和内镜下对病变部位多点取活检，以提高诊断率。     

Characterization of B cell lymphoma in patients with Sjögren's syndrome and hepatitis C virus infection

OBJECTIVE: To characterize the clinical and immunologic patterns of expression, response to therapy, and outcome of patients with Sj?gren's syndrome (SS) and associated hepatitis C virus (HCV) infection who developed B cell lymphoma. METHODS: Various international reference centers constituted a multicenter study group with the purpose of creating a registry of patients with SS-HCV who developed B cell lymphoma. A protocol form was used to record the main characteristics of SS, chronic HCV infection, and B cell lymphoma. RESULTS: Twenty-five patients with SS-HCV with B cell lymphoma were included in the registry. There were 22 (88%) women and 3 (12%) men (mean age 55, 58, and 61 years at SS, HCV infection, and lymphoma diagnosis, respectively). The main extraglandular SS manifestations were cutaneous vasculitis in 15 (60%) patients and peripheral neuropathy in 12 (48%); the main immunologic features were positive rheumatoid factor (RF) in 24 (96%) and type II cryoglobulins in 20 (80%). The main histologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 11 (44%) patients, diffuse large B cell lymphoma in 6 (24%), and follicular center cell lymphoma in 6 (24%). Fifteen (60%) patients had an extranodal primary location, most frequently in the parotid gland (5 patients), liver (4 patients), and stomach (4 patients). Twelve (52%) of 23 patients died after a median followup from the time of lymphoma diagnosis of 4 years, with lymphoma progression being the most frequent cause of death. Survival differed significantly between the main types of B cell lymphoma. CONCLUSION: Patients with SS-HCV and B cell lymphoma are clinically characterized by a high frequency of parotid enlargement and vasculitis, an immunologic pattern overwhelmingly dominated by the presence of RF and mixed type II cryoglobulins, a predominance of MALT lymphomas, and an elevated frequency of primary extranodal involvement in organs in which HCV replicates (exocrine glands, liver, and stomach).     

Morphologic diagnosis of leukaemic B-lymphoproliferative disorders and the role of cyclin D1 expression

PURPOSE: This study analysed the morphologic differences between leukaemic mantle cell lymphoma, follicular lymphoma, nodal marginal zone lymphoma, and diffuse large B-cell lymphoma in peripheral blood. Additionally, we investigated the role of cyclin D1 expression in B-lymphoproliferative disorders. METHODS: The morphologic analysis of the leukaemic cells was performed on cytocentrifuge preparations after separation of mononuclear cells from peripheral blood using a Ficoll-Hypaque density gradient. Cyclin D1 protein expression was studied with the catalyzed signal amplification system. The expression of other markers (CD5, CD23, light chain immunoglobulins) was analysed by the APAAP method. RESULTS: We describe in detail the morphology of the lymphoma cells in eight patients with mantle cell lymphoma, six patients with follicular lymphoma, 11 patients with nodal marginal zone lymphoma, and seven patients with diffuse large B-cell lymphoma. The morphological distinction between these lymphoma cells is a challenge for the haematologist. The investigation of cytocentrifuge preparations of mononuclear cells allows the detection of lymphoma cells also in cases with nondiagnostic white cell differential. Additionally, the immunotype (light chain restriction, CD5, CD23, and cyclin D1) of 108 patients with leukaemic B-lymphoproliferative disorders was studied. Diffuse nuclear expression of cyclin D1 protein (>20%) was specific for mantle cell lymphoma. However, only 6/8 patients showed cyclin-D1 positivity. CONCLUSIONS: The morphologic analysis of lymphoma cells in cytocentrifuge preparations of mononuclear leukocytes in combination with immunocytochemical investigation allows the detection of mantle cells, centrocytes of follicular lymphoma, marginal zone cells, and cells of the diffuse large B-cell lymphoma in peripheral blood. The positivity of cyclin D1 protein improves the differentiation of mantle cells from other lymphoma cells.     

ESHAP方案治疗难治性或复发性恶性淋巴瘤的疗效观察

目的：探讨ESHAP方案对难治性或复发性恶性淋巴瘤(Malignant lymphoma，ML)的疗效。方法：采用ESHAP方案治疗36例难治性或复发性恶性淋巴瘤，其中难治性非霍奇金淋巴瘤(NHL)17例，复发NHL16例，难治性或复发性霍奇金淋巴瘤(HL)3例。结果：12例难治性或复发性ML患者达完全缓解(CR率为33．3％)，10例达部分缓解(PR率为27．8％)；总有效率为61．1％，其中生存最长者43个月，仍处于CR期。毒副作用主要为消化道症状、轻度肝功能异常以及骨髓抑制。结论：ESHAP方案对部分难治性或复发性ML患者仍有效，毒副作用可以耐受。可用于治疗对其他化疗方案无效的难治性或复发性ML。     

Clinical study of 31 patients with primary gastric mucosa-associated lymphoid tissue lymphoma

BACKGROUND: The purpose of the present paper was to investigate the clinical, endoscopic and histological features of 31 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to enable correct, early stage diagnosis. METHODS: A retrospective study was undertaken of 31 patients with gastric MALT lymphoma. The cases were examined immunohistologically with anti-CD(20CY) and CD(45RO) antibodies for further diagnosis. Helicobacter pylori infection was also detected with modified Giemsa staining. RESULTS: Patients with MALT lymphoma were aged between 22 and 73 years (mean, 45.0 years), and the male:female ratio was 11:20. The patients presented with non-specific symptoms, but chronic epigastric pain was the common symptom in a large proportion of the cases. The gastric smaller curvature was involved in 83.9% of cases (26/31) and in 13/31 cases (41.9%) it was confined the antrum. Under endoscopy, large and deep ulcers were similar to cancers in the majority of patients. Only 29.0% of patients were diagnosed by endoscopy on first examination. CD(20CY) were expressed in all cases and CD(45RO) expressed in only one case among 10 cases of indefinite diagnosis. Helicobacter pylori infection was found in 87.1% of patients. CONCLUSIONS: These findings suggest that primary gastric MALT lymphoma has unique clinical, endoscopic and histological features. The diagnosis for primary gastric MALT lymphoma was delayed not only due to the non-specific symptoms but also due to lack of attention to its features. Endoscopy and submucosal multiple biopsy were the principal diagnostic tools in patients with gastric MALT lymphoma. CD(20CY) and CD(45RO) immunological staining are recommended, especially for patients with indefinite diagnosis of gastric MALT lymphoma.     

Pneumothorax associated with lymphoma

Pneumothorax in patients with lymphoma has rarely been reported. We have encountered 8 patients with lymphoma with 17 episodes of pneumothorax; these episodes occurred 3 months to 8 yr in 7 patients after the diagnosis of Hodgkin's disease (HD) and in 1 patient with non-Hodgkin's lymphoma (NHL). The observed incidence of pneumothorax among 1,977 patients with lymphoma was 10-fold higher than expected; this included a significantly higher incidence in patients younger than 30 versus those older than 30 yr of age (1:552 versus 1:5,788 patient-years, p less than 0.001), and a higher incidence in patients with HD than in those with NHL (1:708 versus 1:5,072 patient-years, p less than 0.005). There was a strong suggestion of increased risk for pneumothorax in patients treated with radiotherapy as compared with patients treated without irradiation (1:1,016 versus 0:1,963 patient-years, p = 0.065). Apparent additional contributing factors in 6 patients were lung involvement with lymphoma (n = 2), radiation fibrosis (n = 3), and infection (n = 1). Pneumothorax was persistent in 5 patients, bilateral in 4, and recurrent in 2. The occurrence of pneumothorax in 2 patients heralded death. Management commonly required placement of chest tube (n = 9) or major surgical procedures (n = 5). We conclude that pneumothorax may be more common among patients with lymphoma than previously appreciated. Young age, HD, and probably radiotherapy are predisposing factors. The pneumothoraces associated with lymphoma are more complex and ominous and more difficult to manage than the usual spontaneous pneumothorax. In patients with lymphoma, pneumothorax is likely to be secondary to underlying abnormality of the lung.     

EUS-guided FNA combined with flow cytometry in the diagnoses of suspected or recurrent intrathoracic or retroperitoneal lymphoma

BACKGROUND: Limited data exist on the combined use of EUS-guided FNA (EUS-FNA) and flow cytometry (FC) in the diagnosis of lymphoma. The aim of this study was to evaluate the accuracy of EUS-FNA combined with FC in the diagnosis of primary or recurrent lymphoma. METHODS: This study was a retrospective analysis of a prospective collection of data over a 3-year period. Over 3 years, 29 patients with lesions (n=31) suspicious for lymphoma underwent EUS-FNA and FC. RESULTS: Of the 29 patients, 10 patients had lymphoma and 17 patients had nonlymphoma lesions; for two patients, final diagnosis was indeterminate because of insufficient material for FC. The lymphoma cases included non-Hodgkin's lymphoma (n=6, including 3 recurrences), mucosa-associated lymphoid tissue (MALT) lymphoma (n=2), a non-GI lymphoma with mediastinal lymphadenopathy (n=1), and an uncharacterized lymphoma (n=1). Of the 31 lesions, 8 were true positive, 18 were true negative, and 3 were false negative; for two lesions, we could not determine the final diagnosis. No false-positive results were encountered. The sensitivity, the specificity, and the accuracy of EUS-FNA combined with FC for diagnosing lymphoma were 72.7%: 95% CI [43.3%, 90.3%], 100%: 95% CI [82.4%, 100.0%], and 89.7%: 95% CI [73.6%, 96.4%], respectively. Limitations to this study include a short duration of follow-up and a lack of a surgical criterion standard. CONCLUSIONS: EUS-FNA in combination with FC allows the diagnosis of primary suspected or recurrent lymphoma. It also is an adjunct in staging MALT lymphoma and could direct clinicians toward further investigative procedures.     

Orbital lymphomas: a clinicopathologic study of a rare disease

OBJECTIVE: To evaluate the clinicopathologic features and prognosis of patients with orbital lymphomas. METHODS: Clinical and pathologic data of 35 patients with biopsy-proven orbital lymphoma diagnosed at a tertiary care hospital from 1992 to 2001 were reviewed. Lymphomas were divided into low-grade and high-grade lymphomas. Survival of patients was compared according to age, gender, disease site, extent of disease, tumor grade, and treatment modality by using log rank test. RESULTS: Median patient age was 75 years (23-94) and the male-to-female ratio was 1:2.9. Twenty-three patients (66%) were diagnosed with low-grade lymphoma, and 12 patients (34%) were found to have high-grade lymphoma. Among low-grade lymphomas, marginal zone lymphoma (n=6), follicle center cell lymphoma (n= 6), and small lymphocytic lymphoma (n=5) were common entities, whereas diffuse large cell B-cell lymphoma (n=5) was the most common entity in patients with high-grade lymphoma. Disease was clinically localized in 74% of patients at the time of diagnosis. Radiation alone or with chemotherapy was the primary treatment modality in 83% of patients. All except one patient had an objective response to therapy. Over the median follow-up period of 47 months (range, 1.5-141 months), disease recurred in 37% patients who achieved a complete response. The estimated 5- and 10-year survival rates were 64% and 42%, respectively. Overall, 13 (37%) patients died, 6 with high-grade and 7 with low-grade lymphoma. No clinical variable was found to be prognostically significant with respect to survival. CONCLUSIONS: Orbital lymphoma is a disease of the elderly with a female preponderance. It tends to be localized to the orbit at the time of diagnosis and responds well to local or systemic therapy.     

Triple association between hepatitis C virus infection, systemic autoimmune diseases, and B cell lymphoma

OBJECTIVE: To analyze the clinical characteristics of patients from a Department of Autoimmune Diseases presenting chronic hepatitis C virus (HCV) infection, systemic autoimmune disease, and B cell lymphoma. METHODS: We analyzed the records of 100 consecutive patients with systemic autoimmune diseases and associated HCV infection seen in our department between 1994 and 2000. We retrospectively investigated the development of B cell malignancies after the diagnosis of HCV related autoimmune disease. RESULTS: Six patients with HCV related systemic autoimmune disease presented B cell non-Hodgkin's lymphoma (NHL). These patients fulfilled the diagnostic criteria for Sj?gren's syndrome (n = 4) and polyarteritis nodosa (PAN; n = 2). Four patients were female and 2 male, with a mean age at lymphoma diagnosis of 62 years (range 45-78). The main immunologic markers were hypocomplementemia in all patients and cryoglobulinemia in 5 (83%). Primary extranodal localization of lymphoma was observed in 3 (50%) patients: prostate (n = 1), liver and ovary (n = 1), and ocular annexa (n = 1). Clinically, NHL was classified as indolent lymphoma in 3 patients and aggressive lymphoma in 3. NHL histologic types were diffuse large cell lymphoma (n = 4), extranodal marginal zone B cell lymphoma (n = 1), MALT lymphoma (n = 1), and lymphoplasmacytic lymphoma (n = 1). CONCLUSION: We describe 6 patients with a triple association of HCV infection, systemic autoimmune disease, and NHL. Characteristics of these patients included a high prevalence of cryoglobulinemia (that clearly contributes to fulfillment of diagnostic criteria for PAN) and an elevated frequency of primary extranodal involvement. We recommend careful evaluation of patients with B cell NHL to detect silent autoimmune or chronic viral diseases. This triple association reinforces the suspected links between autoimmunity, infection, and cancer.