IOEP方案治疗20例难治性晚期非何杰金淋巴瘤的初步疗效

本研究报告应用IOEP方案（异环磷酰胺、长春新碱、鬼臼驻乙叉甙、强的松）治疗20例难治性恶性淋巴瘤的临床疗效。全部病例均经病理学证实。治疗结果：全组总有效率为75％，其中，完全缓解率占45％（9／20），部分缓解率为30％（6／20）。主要毒副应为消化道反应，白细胞降低及脱发，无致死性毒副反应发生。     

MUM1/IRF4在恶性淋巴瘤中的表达及其意义

目的通过检测恶性淋巴瘤组织中MUM1（multiple myeloma oneogene1）／IRF4（imerferon regulatory factor4）蛋白的表达，探讨MUM1／IRF4在恶性淋巴瘤的诊断及细胞起源中的意义。方法应用免疫组织化学S-P法，检测84例恶性淋巴瘤标本中MUM1／IRF4蛋白的表达。结果恶性淋巴瘤MUM1蛋白总阳性表达率为66．7％（56／84），其中霍奇金淋巴瘤阳性表达率为100.0％（14／14），非霍奇金淋巴瘤阳性表达率为60．0％（42／70）。在70例非霍奇金淋巴瘤中，B细胞淋巴瘤阳性表达率为52．0％（26／50），T细胞淋巴瘤阳性表达率为80.0％（16／20）。结论霍奇金淋巴瘤H／RS细胞可能来源于B细胞，在目细胞淋巴瘤中MUM1的表达提示该细胞处于分化的终末阶段，在T细胞淋巴瘤中MUM1的表达可能与细胞的活化有关。     

175例鼻腔非何杰金淋巴瘤临床病理及免疫组化分析

目的：探讨鼻腔非何杰金淋巴瘤（NHL）的临床病理及免疫级化特点。方法：收集本院175例鼻腔NHL的临床病理资料并利用免疫组化（ABC法）进行分析。结果：本组病例男女性别之比为3.5：1，平均年龄46.6岁，其中T细胞性淋巴瘤146例（占83％）；B细胞性淋巴瘤29例（占17％）。100例免疫组化标记，瘤细胞表达T细胞分化抗原的有81例；表达B细胞分化抗原有19例；无一例肿瘤细胞表达Mac-387、LYS、AAT。结论：鼻腔NHL以高度恶性T细胞性为多见，且临床情况特殊，真正的组织细胞性淋巴瘤非常罕见。     

133 例恶性淋巴瘤骨髓细胞学分析

目的:探讨恶性淋巴瘤骨髓浸润的临床特点。方法:回顾性分析133 例经病理确诊的恶性淋巴瘤病例,分析其骨髓浸润情况。结果:133 例恶性淋巴瘤患者中骨髓受累率为21.8%（29/133）;在骨髓受累的病例中,淋巴肉瘤性白血病、骨髓侵犯、淋巴瘤细胞比例未达5% 的病例分别占31.0%（9/29）、55.2%（16/29）和13.8%（4/29）。 在29例骨髓受累病例中,B 细胞淋巴瘤占55.2%（16/29）,T/NK细胞淋巴瘤占41.4%（12/29）,霍奇金病占3.4%（1/29）。 T/NK细胞淋巴瘤的骨髓受累率为37.5%（12/32）,比B 细胞淋巴瘤要高18.2%（16/88）,两组具有统计学差异。结论:恶性淋巴瘤骨髓浸润比例高,不同的病理学类型骨髓受累的风险不一,总体而言T 细胞淋巴瘤的骨髓浸润率更高,而且以淋巴肉瘤性白血病多见,骨髓细胞学检查对恶性淋巴瘤的正确分期、治疗方案的选择和预后判断有重要的意义。      

33例小肠非霍奇金淋巴瘤治疗分析

目的探讨小肠非霍奇金淋巴瘤的临床特点、诊断、治疗和预后。方法回顾性分析33例小肠非霍奇金淋巴瘤，其中滤泡型裂细胞性2例，弥漫型裂细胞性7例，弥漫型裂-无裂细胞性5例，弥漫型无裂细胞性6例，免疫母细胞性1例，黏膜相关淋巴组织淋巴瘤2例，弥漫性大B细胞淋巴瘤9例，另有1例为T细胞淋巴瘤。Ann Anbor分期ⅠE期12例，ⅡE期15例，ⅣE期6例。手术治疗33例，29例行根治术，另4例行姑息性切除术。26例行术后放疗，移动条照射12例，全腹盆腔大野照射14例；中位总剂量2543．5cGy。术后化疗33例，其中CHOP方案17例，COMP方案6例，COP方案3例，MINE方案2例，COPP方案3例，BACOP方案2例。结果5年总生存率和无病生存率分别为48％和39％，中位值分别为47、23个月。各期的生存率分别为ⅠE期42％，ⅡE期67％，ⅣE期17％。结论小肠淋巴瘤多为ⅠE、ⅡE期，病理以中、高度恶性为主，治疗多采用以手术为主的综合治疗，术后放疗及化疗可提高生存率。     

自体外周血干细胞移植治疗恶性淋巴瘤的临床研究

目的分析自体外周血造血干细胞移植（APBSCT）治疗恶性淋巴瘤的临床疗效及安全性。方法自1995年12月至2005年12月，采用APBSCT联合大剂量化疗治疗恶性淋巴瘤31例。平均4周期常规诱导化疗后行APBSC动员及采集。动员方案：非霍奇金淋巴瘤（NHL）病人采用常规剂量CHOP方案，霍奇金淋巴瘤（HL）病人采用高剂量单药CTX4g／m^2。预处理方案：异环磷酰胺（IFO）12g／m^2CTX4g／m^2，阿糖胞苷（Ara—C）4．5g/m^2，足叶乙甙（Vp-16）0．75g／m^2。移植后对原发灶直径大于4cm或有肿瘤残留的病灶给予局部补量放疗。结果31例病人移植后缓解时间为1N108mo，中位缓解期43mo。其中1年无病生存26例（83．9％），2年23例（74．1％），3年21例（67．7％）。全组无移植相关死亡。结论APBSCT联合大剂量化疗治疗恶性淋巴瘤的疗效明显优于常规化疗且安全性高值得推广。     

ProMACE／CytaBOM方案治疗中高度非霍奇金淋巴瘤

目的：研究ＰｒｏＭＡＣＥ／ＣｙｔａＢＯＭ方案治疗中、高长恶性非霍奇金淋巴瘤的临床疗效及不良反应。方法：采用ＰｒｏＭＡＣＥ／ＣｙｔａＢＩＯＭ方案治疗非奇金 。其中弥漫性大细胞型２１例，弥漫性小裂细胞型３例弥漫性大小细胞混合型４例，免疫母细胞型３例，淋巴母细胞型２例，小无裂细胞型１例。恶性程度为中高度。分期为Ⅱ～Ⅳ期，结果：ＣＲ２３例，占６７．６％；ＰＲ６例，占１７．６％。有效率为８５．３％。主要毒副     

高度恶性非霍奇金淋巴瘤的治疗

高度恶性非霍奇金淋巴瘤（工作分类）主要包括：弥漫性小无裂细胞性淋巴瘤（ Burkitt′ s, Burkitt′ s-like）和淋巴母细胞性淋巴瘤。这类淋巴瘤占成人非霍奇金淋巴瘤（ non-Hogdkin′ s-lymphoma,NHL）的 10％以下,儿童青少年 NHL的 75％ [1]。恶性程度高,进展快,死亡率高。但积极治疗能获得较高的治愈率。目前国外发达国家已获得 70％以上的治愈率。本文主要概述国外有关这方面的治疗进展。     

B淋巴瘤6号染色体微卫星不稳定性及杂合性缺失

目的：探讨6号染色体微卫星不稳定性（microsatellite instability，MSI）及杂合性缺失（loss of heterozygosity，LOH），碱基错配修复系统GTBP和hMLH1基因蛋白在B细胞淋巴瘤（B cell non-hodgkin’s lymphoma，B-NHL）发生学上的意义。方法：选取6号染色体上7对多态微卫星标记，结合PCR及银染技术，采用凝胶成像图象分析系统，分别检测58例B-NHL染色体微卫星MSI及LOH。对其中23例BNHL细胞进行EnVinsion法检测MMR的功能基因GTBP、hMLH1的表达情况。结果：弥漫性大B细胞淋巴瘤（diffuse large B-celllymphoma，DLBCL）与滤泡性淋巴瘤（follicular lymphoma，FL）中GTBP和hMLH1蛋白表达差异无统计学意义，P值分别为0．98和1．30。原发生于淋巴结内与淋巴结外的GTBP、hMLH1蛋白表达差异无统计学意义，P值分别为0．54和0．67。GTBP蛋白在高、低度恶性表达之间差异无统计学意义，P=1．00；而hMLH1蛋白表达在低度恶性较高度恶性高，P=0．99。在位点D6S275 MSI的发生率为7．5％（4／53），其中包括DLBCL2例，FL和BCLL／SLL各1例，LOH总的发生率达66．0％（35／53），其中包括DLBCL19例（19／21，90．5％），FL8例（8／13，61．5％），B-CLL／SLL8例（8／19，42．1％），DLBCL的LOH率同B-CLL／SLL和FL相比，差异有统计学意义，P=10．60。结论：hMLH1和GTBP错配修复基因蛋白表达与BNHL组织学类型、肿瘤的发生部位可能无关系。位点D6S275可能存在一个抑癌基因，该基因的缺失以及与错配修复基因hMLH1突变的关系对B细胞淋巴瘤的发生作用有待进一步研究。     

10例原发性宫颈淋巴瘤临床分析

目的探讨宫颈淋巴瘤的发病、诊断、治疗及预后。方法临床资料回顾性分析。结果本组病例占同期宫颈恶性肿瘤的０．９％,１０例患者平均年龄４３．６岁,７例有癌肿家族史,临床症状以阴道出血和／或白带增多为主,肿瘤形态为息肉型（４例）、糜烂型（４例）和结节型（２例）。按ＦＩＧＯ分期：Ⅰｂ期８例,Ⅱｂ期１例,Ⅳ期１例。本组病例均经病理确诊,病理类型上属非霍奇金淋巴瘤（ＮＨＬ）,Ｂ细胞性,其中弥漫型裂细胞性３例,裂－无裂细胞性４例。１０例患者采用手术和化疗为主的综合治疗,随访期３～６６个月,除１例术后４１个月腋下转移外,９例无瘤生存。结论如果发现早,治疗适当,宫颈淋巴瘤疗效并非很差。     

Clonal T cell population in angioimmunoblastic lymphadenopathy and related lesions

The arrangements of the T cell receptor (TCR) beta genes were studied in lymph node specimens with the histological characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), AILD-like T cell lymphoma (AILD-T), T-zone lymphoma, or Lennert's lymphoma. Eight of 11 cases with AILD or AILD-T showed clonal rearrangements of TCR beta genes: all three AILD cases showed clonal rearrangements of TCR beta genes, while five of 8 AILD-T cases exhibited clonal rearrangement patterns. Malignant lymphoma evolved in one AILD case showed the same rearrangement band of TCR beta genes as its primary AILD lesion. The rearrangement of TCR beta genes was also observed in 2 out of 3 cases with T-zone lymphoma and 2 out of 2 cases with Lennert's lymphoma. None of the cases studied, except one AILD-T case, exhibited clonal rearrangements of immunoglobulin heavy chain genes. The results suggested that a significant proportion of AILD, AILD-T, T-zone lymphoma and Lennert's lymphoma cases are malignancies of peripheral T cell origin.     

Fine-needle aspiration biopsy of peripheral T-cell lymphomas. A cytologic and immunophenotypic study of 33 cases

INTRODUCTION: Peripheral T-cell lymphoma (PTCL) accounts for 10-20% of all non-Hodgkin lymphomas in the United States. In this study, the authors reviewed the cytologic and immunophenotypic findings of 33 fine-needle aspirations (FNAs) of PTCL. METHODS: Thirty-three FNAs from 26 patients (12 females and 14 males) with PTCL were identified during 1991-1999. The patients' age ranged from 19 to 96 years. Immunophenotyping was performed in 24 cases by using either flow cytometry (FC; 21 cases) or immunocytochemistry (IC; 3 cases). Follow-up included review of prior or current histology and clinical records. RESULTS: Nine cases were associated with mycosis fungoides, three cases were classified as T-cell chronic lymphocytic leukemia, and two were angioimmunoblastic adenopathy (AILD)-like T-cell lymphoma. The remaining 19 were classified as PTCL, not otherwise specified. The latter consisted of eight mixed cell variant, eight large cell variant, and three anaplastic variant. One of the mixed cell variant and one of the large cell variants contained numerous epithelioid histiocytes (Lennert lymphoma). Thirty (91%) cases had a definitive diagnosis of malignant lymphoma. Twenty-two cases (2 IC and 20 FC) showed a predominant population of T lymphocytes without a monoclonal B-cell population. In addition, FC revealed an aberrant expression of T-cell markers in 13 cases. Two cases were interpreted as "atypical lymphoid population"; one case was an AILD-like T-cell lymphoma, and the other case was PTCL, large cell type. One case initially was interpreted as granulomatous lymphadenitis; subsequent biopsy revealed PTCL, Lennert type. CONCLUSIONS: Peripheral T-cell lymphoma is a heterogeneous group of lesions with diverse cytomorphology. Cytologic analysis and immunophenotyping is an accurate method of diagnosing peripheral T-cell lymphoma.     

Treatment of non-Hodgkin's lymphoma with NK-631 (peplomycin)--with special reference to the effect on T and non-T cell lymphomas

NK-631 (Peplomycin) has an anti-tumor spectrum, equivalent to or higher than its analogue bleomycin and low toxicities to the lungs. Fourteen patients with advanced non-Hodgkin's lymphoma received NK-631 10 to 30 mg once or twice a week. As the results, there were 57.1% response rate of all patients. The response rate according to the immunologic classification were 100%(6/6 cases) for patients with non-T cell lymphoma and 25%(2/8 cases) for patients with T-cell lymphoma. On the other hand, we observed some toxicities such as transient fever in 64.3%, G-I tract symptoms in 21.4%, skin toxicities in 21.4% and pulmonary fibrosis in one case. This agent is considered to be one of the useful agents to non-Hodgkin's lymphoma especially non-T cell lymphoma.     

Nasal lymphomas in Japan: a high prevalence of Epstein-Barr virus type A and deletion within the latent membrane protein gene

The majority of nasal lymphomas are of the natural killer (NK)/T cell lineage. We analyzed 33 specimens of nasal lymphoma from Japanese patients for Epstein-Barr virus (EBV). Phenotypic and genetic analyses showed 28 cases with NK/T cell type and 5 cases with B cell type. All NK/T lymphomas were of pleomorphic cell type except 2 large cell (centroblastoid) and one lymphoblastic lymphoma. All cases with nasal B cell lymphoma were of large (centroblastoid) cell type. EBV was detected in all cases of NK/T cell type with the exception of one lymphoblastic case, and was monoclonally integrated in all cases examined (14/14 cases). All but one case had subtype A of EBV infection with 30-base paired deleted LMP-1 gene. One case of B cell lymphoma showed the presence of EBV infection with subtype A and deletion of LMP-1. Our results indicate that the majority of nasal lymphomas in Japanese patients are of the nasal NK/T cell type, have pleomorphic morphology, a high prevalence of EBV with a monoclonal integration, subtype A and deleted LMP-1 gene. In contrast, nasal B cell lymphoma showed monomorphic appearance and rare EBV infection.     

Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased "take" rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid lymphoma and T-cell diffuse lymphoblastic lymphoma became transplantable.     

Ki-1-positive large cell lymphomas, a heterogenous group of neoplasms. Morphologic, immunophenotypic, genotypic, and clinical features of 24 cases.

Clinical and pathologic features of 24 patients with large cell lymphomas that expressed the activation antigen Ki-1 are described. Phenotypic and/or genotypic studies characterized these neoplasms as T-cell (16 cases), B-cell (six cases), or null cell (two cases) type. Males predominantly were affected. Age of patients ranged from 19 to 73 years, with a bimodal distribution, with peaks in the third and seventh decades. Lymphadenopathy was present in nearly all patients. Extranodal involvement, including skin, soft tissue, bone, central nervous system, lung, or small intestine was observed in a total of 54% of the patients, either at presentation or during the course of disease. "Prototypic" features of large cell anaplastic lymphomas were observed for eight T-cell lymphomas, with morphologic heterogeneity noted for the remainder. Eight patients, all with T-cell neoplasms (only one with prototypic morphology), have died of lymphoma (median survival, 5 months). An antecedent history of a lymphoproliferative disorder (mycosis fungoides, B-cell lymphoma, immunoblastic lymphadenopathy) was apparent in seven patients. An 8-year history of Crohn's disease occurred in one patient with a T-cell lymphoma involving small intestine. Phenotypically, loss of one or more markers was typically noted for T-cell neoplasms. Leukocyte common antigen was detected in all cases, although partial loss of immunoreactivity was noticed in some cases. Nearly all cases evaluated for Ia antigen or alpha-1-antichymotrysin were reactive. Eleven of 16 T-cell, two of six B-cell, and two null cell lymphomas expressed epithelial membrane antigen. Ki-1-positive large cell lymphomas are characterized by clinical, morphologic, and immunophenotypic heterogeneity.     

Primary bladder lymphoma: management and outcome of 12 patients with a review of the literature

Primary bladder non-Hodgkin's lymphoma (NHL) is rare. Optimal management remains controversial. Using the Scotland and Newcastle lymphoma group database, 12 patients with primary bladder lymphoma were identified between 1980 and 2001, the largest single group of patients available to date. Histology and immunocytochemistry was reviewed in 9 of the 12 cases. Six cases were low-grade extranodal marginal zone lymphoma, 4 diffuse large B-cell lymphoma, one an ALK 1 positive anaplastic large cell lymphoma (ALKoma) and one a low-grade lymphoma unspecified. Two patients (low-grade NHL) were treated with oral antibiotics (n = 1) or diathermy (n = 1) alone with complete resolution of disease. One patient with high-grade NHL gained complete remission without conventional therapy. Nine patients were treated with single or combined modality surgery, chemotherapy and/or radiotherapy. Overall survival was 75%, mean follow up of 4.8 (range 1 - 10) years. A review of 88 additional cases in the literature support the findings that primary bladder lymphoma is associated with a good prognosis. Patients with low-grade extranodal marginal zone lymphoma may respond well to simple therapies. Patients with diffuse large B-cell lymphoma respond well to first-line chemotherapy regimens. Ureteric obstruction and acute renal failure are serious complications. Repeat cystoscopy is mandatory for follow-up.     

T细胞非霍奇金淋巴瘤多种治疗方案的疗效比较

 目的　探讨CHOP、CTOP和CTOPL方案以及干扰素治疗T细胞非霍奇金淋巴瘤（NHL）的治疗效果。方法　用三种化疗方案治疗T细胞NHL 40例,CHOP方案治疗15例,CTOP方案治疗18例,CTOPL方案治疗7例,用干扰素治疗皮肤T细胞NHL 6例。结果　CHOP方案组化疗后CR 10例（66.7 %）,PR 2例（13.3 %）,PD 3例（20.0 %）。CTOP方案组CR 13例（72.2 %）,PR 3例（16.7 %）,PD 1例（5.6 %）,早期死亡1例（5.6 %）。CTOPL方案组CR 5例（71.4 %）,PR 2例（28.6 %）。三组之间CR、PR和PD比较, 差异均无统计学意义（P＞0.05）。干扰素治疗组病情均完全缓解。CHOP方案化疗长期生存2例,CTOP方案4例,CTOPL方案3例,干扰素治疗长期生存4例。结论　CTOP和CTOPL方案是目前临床上治疗T细胞NHL较好的方案,但如何克服T细胞NHL的耐药性仍需在临床上进一步探讨。     

侵袭型非霍奇金淋巴瘤合并纯红细胞再生障碍性贫血

目的:研究侵袭性非霍奇金淋巴瘤并发纯红细胞再生障碍性贫血(PRCA)的临床特点和治疗结果。方法:报告两例分别并发于非特指型外周T细胞淋巴瘤(PTCL-NOS)和弥漫大B细胞淋巴瘤(DLBCL)的PRCA,并复习相关文献。结果:在联合化疗治疗后,DLBCL及其相关的PRCA均获完全缓解,而PTCL-NOS虽获缓解,但其相关的PRCA未好转,加用泼尼松治疗后PRCA缓解。结论:NHL相关的PRCA在联合化疗或免疫抑制治疗后可获完全缓解,且可不需维持治疗。     

Evaluation of rIFN-gamma in the treatment of lymphoma and melanoma of the skin by systemic and intralesional administration

This study evaluated the clinical effect of rIFN-gamma for the treatment of lymphoma and melanoma of the skin by systemic intravenous and intralesional administration. By intravenous drip infusion, one of two cases of mycosis fungoides (stage IV) showed CR of skin lesions by administration of a total of 160 X 10(6) units, 4 or 8 X 10(6) units, every other day for 3 months. The remaining case was, however, in a state of PD. Intralesional administration of rIFN-gamma to six cases of cutaneous lymphoma, including three cases of mycosis fungoides, two cases of cutaneous T cell lymphoma, and one case of adult T cell lymphoma, resulted in three cases of CR, two cases of MR and one case of PD. In contrast, four cases of malignant melanoma, two of which received systemic administration and two intralesional administration, did not show any obvious clinical response, one showing PR and the other three PD. Histopathological examination of skin lesions before and after administration of rIFN-gamma indicated that the cutaneous lymphoma lesions were initially infiltrated by lymphocytes and macrophages, and that later on, they were free from tumor cells. Our study indicates that rIFN-gamma appears to provide a new modality for the treatment of cutaneous lymphoma by systemic and intralesional administration.