EBV阳性的老年弥漫大B细胞淋巴瘤6例临床分析

目的：分析 EBV 阳性的老年弥漫大 B 细胞淋巴瘤临床特点。方法：采用 EBV 编码微小 RNA（EBV encoded miRNA,EBERs）原位杂交检测方法确定 EBV 感染的老年弥漫大 B 细胞淋巴瘤6例。结果：6例患者中男、女各3例;中位发病年龄为59.2（50~66）岁;疾病分期在Ⅱ期的有3例,Ⅳ期3例;IPI 评分<2分的患者有3例,≥2分的患者3例;有 B 症状的患者3例,无 B 症状的患者3例;ECOG <2分的患者4例,ECOG≥2分的患者2例;LDH 升高的患者3例,LDH 正常的患者3例。生发中心外的患者3例,生发中心内的患者3例;CD30阳性的患者5例,CD30阴性的患者1例。原发于淋巴结外的患者有5例,原发于淋巴结的患者1例。6例患者治疗均采用 CHOP 样方案,其中1例应用 R - CHOP 方案化疗6周期,疾病达 PR,1例应用CHOP 方案化疗6周期,疾病达 CR,2个月后疾病进展,给予放疗及 CHOP 方案化疗2周期效果不佳死亡,1例应用 R - CHOP 方案化疗4周期,疾病完全缓解后应用 R 单药维持治疗,1例应用 R - CHOP 方案化疗4周期疾病达 PR,再次给予 R - CHOPE 方案治疗后疾病快速进展死亡,1例应用 CHOPE 方案化疗5周期后疾病达 PR,1例应用 R - CHOP 方案化疗2周期后放疗疾病进展死亡。上述病例死亡3例,部分缓解2例,完全缓解1例,中位生存时间为10个月。结论：EBV 阳性的老年弥漫大 B 细胞淋巴瘤患者发病率较低,对治疗的敏感性差,即使疾病达到完全缓解亦很快进展死亡,且常以淋巴结结外侵犯为主,伴有 CD30阳性,本实验由于病例有限,仍需多家中心联合统计,进一步探究治疗 EBV 阳性的老年弥漫大 B 细胞淋巴瘤具有针对性的有效治疗方案,最大程度的改善患者预后。     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

Incidence and pathology of primary brain lymphoma in Hong Kong Chinese patients

Primary brain lymphoma (PBL) is an uncommon extranodal lymphoma. Its incidence is rapidly increasing in both immunocompromised and immunocompetent patients in Western countries. Eighteen cases of PBL were identified during a 16-year period among HIV negative patients in Queen Mary Hospital, Hong Kong. One case of post-transplantation lymphoproliferative disease (PTLD) was positive for Epstein Barr virus (EBV) encoded RNA (EBER) by in situ hybridization. All the remaining 17 immunocompetent cases were classified as diffuse large B-cell lymphoma, except for one case of Burkitt's lymphoma. EBER expression was negative in all 13 cases tested. Immunostaining for bcl-2 and bcl-6 was positive in 8/11 and 6/11 cases tested, with heterogeneous combination of expression and intensity. The incidence rate of PBL in immunocompetent patients was stable at 1.03 per million per year. The incidence of PBL in post transplantation (0.16%) and HIV related setting (0.29%) is also low in Chinese. PBL in Chinese patients is almost uniformly represented by EBV negative, diffuse large B-cell lymphoma, confined to the brain. However, the molecular pathogenesis may be heterogeneous.     

Epstein-Barr virus associated diffuse large B-cell lymphoma complicated by autoimmune hemolytic anemia and pure red cell aplasia.

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.     

Malignant lymphoma in patients with rheumatic diseases other than Sjogren's syndrome: a clinicopathologic study of five cases and a review of the Japanese literature

We conducted clinicopathologic and immunohistochemical analysis of five patients with malignant lymphoma complicating rheumatic diseases other than Sjogren's syndrome, and reviewed 26 cases of similar lesions reported in the Japanese literature over a 17-year period. All five patients were women ranging in age from 31 to 74 years (mean 55 years). Two of them fulfilled the diagnostic criteria for systemic lupus erythematosus, two for dermatomyositis and one for progressive systemic sclerosis. The use of immunosuppressive drugs before the onset of malignant lymphoma was recorded in four patients. All the biopsied or resected specimens showed non-Hodgkin's lymphoma of B-cell phenotype. Three were nodal in origin (one diffuse mixed, one diffuse large cell and one immunoblastic) and two were extranodal (one low-grade B-cell lymphoma of mucosa-associated lymphoid tissue and one diffuse large cell). In three of four cases examined, Epstein-Barr virus-encoded small RNAs were identified in a small to large number of the lymphoma cells by in situ hybridization. Our study showed that the clinicopathological features of malignant lymphomas complicating rheumatic disease in Japan were similar to those in England and the USA. Furthermore, our findings suggested no evidence for a causative association between iatrogenic immunosuppression due to methotrexate therapy and the development of EBV-related lymphoid neoplasms.      

24例原发纵隔大B细胞淋巴瘤的临床分析并文献复习

背景与目的:原发纵隔大B细胞淋巴瘤(primary mediastinal large B-cell lymphoma,PMBCL)是弥漫大B细胞淋巴瘤的一种亚型,发病率较低。本研究旨在分析其临床特征,探讨合理的治疗模式及预后因素。方法:收集1995年5月至2005年9月于福建省肿瘤医院确诊并接受治疗的24例PMBCL患者的临床资料并行回顾性分析,同时结合文献加以讨论。结果:24例患者中男性16例,女性8例,年龄12～81岁,30岁以下13例。临床Ⅰ Ⅱ期20例,Ⅲ期1例,Ⅳ期3例。有纵隔巨块13例,伴上腔静脉综合征10例,邻近器官受侵14例,乳酸脱氢酶升高15例。初治时11例采用联合化放疗,10例采用单纯化疗,3例采用单纯放疗,完全缓解率41.7%,总有效率91.7%,中位生存期89个月,3年总生存率68.8%,其中初治时达完全缓解者至随访结束时均生存,国际预后指数(international prognostic index,IPI)在本组中未显示预后,多因素分析提示纵隔巨块与预后相关。结论:PMBCL在本组中男性多见,临床表现凶险,须尽快明确诊断。蒽环类为主的化疗联合放疗可取得较好疗效,初治时获得完全缓解尤为关键,伴有巨块者预后差。     

Gastrointestinal lymphoma

Opinion statement The ability to make treatment recommendations for patients with gastrointestinal lymphoma is hampered by a lack of prospective trials and by a lack of uniformity in classification and staging. Patients with gastric diffuse large B-cell lymphoma have traditionally been treated with surgery and many physicians continue to recommend this approach. However, recent data suggest that these patients can be treated with combination chemotherapy regimens in the same manner as patients with nodal presentations of diffuse large B-cell lymphoma. There is evidence to suggest that adjuvant radiotherapy may improve the outcome for these patients. The recognition that extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue is a distinct clinicopathologic entity and the elucidation of the pathogenic role of Helicobacter pylori has revolutionized the treatment of these gastric lymphomas. Patients with localized disease should be managed with antibiotic therapy initially. Radiation therapy is extremely effective for these patients, but it should probably be reserved for patients who fail anti-H. pylori treatment.     

Primary extranodal lymphomas of stomach: clinical presentation,diagnostic pitfalls and management

Gastrointestinal lymphoma is the most common form of extranodal lymphoma, accounting for 30%–40% of cases. The most commonly involved site is the stomach (60%–75% of cases), followed by the small bowel, ileum, cecum, colon and rectum. The most common histological subtypes are diffuse large B-cell lymphoma (DLBCL) and marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Helicobacter pylori infection has been implicated in the pathogenesis of MALT gastric lymphoma, but its role in gastric diffuse large B-cell non-Hodgkin's lymphoma (NHL) is controversial. The therapeutic approach for patients with gastric NHL has been revised over the last 10 years. Conservative treatment with anthracycline-based chemotherapy alone or in combination with involved-field radiotherapy has replaced gastrectomy as standard therapy in cases with DLBCL. Additionally, MALT lymphomas are mainly treated with antibiotics alone, which can induce lasting remissions in those cases associated with H. pylori infection. Nevertheless, various therapeutic aspects for primary gastric lymphomas are still controversial and several questions remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as H. pylori eradication in histological aggressive subtypes warrants better clarification.     

Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx.

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL.     

171例淋巴瘤病变组织中EB病毒表达情况的分析

目的:探讨不同类型淋巴瘤与EB病毒(Epstein-Barr virus,EBV)感染的关系。方法:收集淋巴瘤组织171例,包括弥漫大B细胞淋巴瘤(DLBC)106例;结外NK/T细胞淋巴瘤,鼻型22例;霍奇金淋巴瘤(HL)19例;血管免疫母细胞性T细胞淋巴瘤(AITL)13例;黏膜相关淋巴组织B细胞淋巴瘤(MALT)11例。应用EBV Lmp-1单抗免疫组化(IHC)和生物素标记的EBER1寡核苷酸探针原位杂交(ISH)分析EBV感染与淋巴瘤的关系。结果:淋巴瘤组织中EBV Lmp-1蛋白与EBER1 mRNA总阳性率分别为11.1%(19/171)、25.7%(44/171)。其中AITL为30.8%(4/13)、61.5%(8/13);HL为47.4%(9/19)、57.9%(11/19);结外NK/T细胞淋巴瘤为22.7%(5/22)、81.8%(18/22);DLBC为0.94%(1/106)、5.7%(6/106);MALT为0(0/11)、9.1%(1/11)。结果显示EBV在DLBC及MALT中的表达率低于AITL、HL及结外NK/T细胞淋巴瘤,差异有统计学意义(P0.05);且原位杂交检测EBER1 mRNA比免疫组化检测Lmp-1蛋白更为敏感(P0.01)。结论:EBV感染与淋巴瘤有密切关系,不同类型淋巴瘤与EBV感染的关系有差异。     

Aktuelle Therapiestrategien bei follikul?ren Lymphomen

Follicular lymphomas are the second most frequent lymphoma entity following diffuse large cell B-cell lymphoma. The clinical course is slowly progressive so that they belong to the group of indolent lymphomas. For the few patients where the disease is diagnosed in localized stages I or II radiotherapy is indicated. In advanced stages III and IV a watch and wait strategy is indicated when there is a lack of clinical symptoms. If treatment is indicated immunochemotherapy followed by a 2-year rituximab maintenance comprises the standard of care.     

含培门冬酶化疗方案拯救性治疗难治性淋巴瘤的效果观察

目的 观察培门冬酶联合化疗治疗难治性淋巴瘤的效果.方法 回顾性分析28例难治性淋巴瘤患者接受含培门冬酶化疗方案治疗的结果.结果 28例患者中位年龄36岁,治疗前疾病状态为部分缓解（PR）4例,疾病稳定（SD）6例,疾病复发或疾病进展（PD）18例,治疗后患者完全缓解（CR）5例,PR 15例,SD 4例,PD 4例,总有效（CR＋PR）率为71.4％.16例T细胞性淋巴瘤患者治疗有效率达81.3％（13/16）.10例弥漫大B细胞淋巴瘤患者治疗有效率达60.0％（6/10）.治疗前无骨髓浸润者或无乳酸脱氢酶升高者治疗有效率更高.主要不良反应为骨髓抑制、消化道反应、凝血异常.结论 培门冬酶联合化疗方案可作为拯救性治疗难治性淋巴瘤的选择之一.     

B-cell lymphoma possessing t(14;18)(q32;q21)in a patient with rheumatoid arthritis receiving methotrexate treatment

There is evidence of a slight increase in malignant lymphoma among rheumatoid arthritis(RA)patients receiving methotrexate( MTX). Increased rates of lymphoma have been attributed to reactivation of the Epstein-Barr virus(EBV). A 72-yearold woman was admitted to our hospital for generalized lymph adenopathy. She suffered from RA and has been treated with MTX for 7 years; the total amount of MTX received was around 2, 700 mg. The cervical lymph node revealed a diffuse proliferation of large atypical lymphocytes. An immunophenotype revealed CD10+, CD19+, CD20+, and k+. The chromosome analysis showed a complex abnormality containing t(14;18)(q32;q21). The tumor cells were positive for EBV sequences by in situ hybridization(ISH). A rituximab containing regimen was effective, but a systemic relapse occurred 4 years later. The biopsied sample was diagnosed as diffuse large B-cell lymphoma. FISH analysis revealed positive for t(14;18)(q32;q21), however, EBV was negative using ISH. In general, the concurrence of t(14;18)(q32;q21)and EBV in the B-cell lymphoma is rare. In addition, the negative change in EBV in the relapsed lymphoma cells revealed a quite rare phenomenon.     

Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I-II, diffuse large B-cell lymphoma of the stomach

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by radiotherapy is regarded as standard care for localized aggressive lymphoma; however, prospective confirmation of its applicability to localized primary gastric lymphoma is inadequate, and most patients in Japan have been initially treated with gastrectomy. We conducted a multicenter phase II study to evaluate the feasibility and efficacy of the non-surgical treatment. Eligibility criteria required primary gastric diffuse large B-cell lymphoma, stage I-II(1), age 20-75, performance status 0-1 and adequate organ function. Treatment consisted of three cycles of CHOP followed by radiotherapy 40.5 Gy. Fifty-five patients were enrolled between December 1999 and February 2003, and 52 eligible patients were analyzed. Patient characteristics were as follows: median age, 61 years; 28 men, 24 women; 36 with stage I, 16 with stage II(1); 47 with a low International Prognostic Index (IPI) and five with a low-intermediate IPI. All but one patient completed planned treatment. No serious complications including massive hemorrhage or perforation were observed. A complete response was achieved in 48 of the 52 patients (92%, 95% confidence interval: 82-98%) and progressive disease in three. Two patients underwent salvage gastrectomy due to disease persistence or recurrence. With a median follow-up period of 28 months, 2-year progression-free and overall survivals were 88 and 94%, respectively. CHOP followed by radiotherapy is safe and highly effective in localized gastric diffuse large B-cell lymphoma. This organ-preserving treatment should be considered as a very reasonable therapeutic option.     

ALK-positive diffuse large B-cell lymphoma: report of three cases

Diffuse large B-cell lymphoma positive for anaplastic lymphoma kinase (ALK(+) DLBCL) is a rare variant of diffuse large B-cell lymphoma, with characteristic morphological, immunohistochemical and cytogenetic features. Only 34 cases of ALK-positive diffuse large B-cell lymphoma have so far been reported in the literature. We examined three new cases, which showed similar characteristics to previously reported cases, but with peculiar nuclear-membrane staining for ALK protein in one patient and a 5'-ALK gene deletion in another. All of them had stage IV disease at initial presentation, with poor outcomes. The tumour cells showed immunoblastic/plasmablastic histology and were positive for ALK and Oct2, but negative for CD3, CD20, CD79a, CD30 and PAX5. The staining pattern of ALK protein was cytoplasmic in two patients and associated with the nuclear membrane in one patient. Fluorescence in situ hybridization (FISH) analysis using the ALK break-apart probe revealed ALK gene rearrangements in all three patients, with a 5'-ALK gene deletion in one patient. These three cases suggest that different types of cytogenetic aberrations may involve the ALK gene in ALK-positive diffuse large B-cell lymphoma leading to peculiar immunohistochemical staining patterns.     

Ongoing monoclonal B-cell proliferation is not common in gastric B-cell lymphoma after combined radiochemotherapy.

PURPOSE: Gastric marginal-zone B-cell lymphoma (MZBCL) of the mucosa-associated lymphoid tissue (MALT) is associated with chronic Helicobacter pylori gastritis. Stable complete remission (CR) can be induced by H pylori eradication. Whether this is paralleled by cure of the lymphoma remains unclear. Persisting monoclonal bands for immunoglobulin heavy chain variable region (VH) representing the lymphoma clone have been described in up to 50% of patients in CR. This retrospective study investigated whether this phenomenon also occurs after radiochemotherapy. PATIENTS AND METHODS: Biopsy samples of 20 patients receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone and irradiation were analyzed before and after therapy. Study patients had Ann Arbor stage I/II primary gastric cancer, including four cases of MZBCL of MALT type, 12 cases of diffuse large-cell lymphomas (DLCL), and four cases of mixed MALT type/DLCL. Polymerase chain reaction (PCR) for VH rearrangement was performed. Monoclonal PCR products were cloned and sequenced. RESULTS: Fourteen of 20 patients had a monoclonal or oligoclonal band distribution at diagnosis converted into polyclonal pattern after radiochemotherapy. Of the remaining six patients, two were lost to follow-up. One patient did not respond and died of progressive disease. PCR in this patient showed persistent B-cell clonality. In three patients, the initial PCR showed a polyclonal pattern and thus could not be evaluated during follow-up. CONCLUSION: In contrast with H pylori eradication alone, radiochemotherapy results in clearing of monoclonal cells during follow-up. This may result in better elimination of residual lymphoma cells. Further study is needed to determine whether this translates into lower risk of relapse.     

Splenic lymphoproliferative disorders in human T lymphotropic virus type-I endemic area of japan: clinicopathological, immunohistochemical and genetic analysis of 27 cases

Primary splenic involvement in lymphoid neoplasms is rare and the clinicopathologic features of splenic lymphoma are not well described compared to nodal non-Hodgkin's lymphoma (NHL). Here we characterized splenic lymphomas in an human T lymphotropic virus type-I (HTLV-I) endemic area of Japan. To assess the pattern of splenic involvement and evaluate prognosis, we reviewed 27 specimens consisting of 26 splenectomies and one necropsy, which were classified using REAL classification. Cases were divided into primary splenic lymphoma in 11 patients and secondary in 16 patients. The incidence of primary splenic lymphoma was 0.3% (11 of approximately 4,000 malignant lymphomas). Primary splenic lymphomas included 7 diffuse large B cell lymphoma (DLBL), 2 follicular lymphomas (FL), and 1 each of splenic marginal zone lymphoma (SMZL) and anaplastic large cell lymphoma (ALCL). Secondary splenic lymphomas included 6 DLBL, 4 mantle cell lymphoma (MCL), 2 FL, 2 Hodgkin's disease (HD), 1 each of hairy cell leukemia and ALCL. Gross examination showed two patterns of splenic involvement; solid type (formation of large nodular mass, n=16) and disseminated type (multiple nodules with diffuse infiltration but no large nodular formation, n=10). The type could not be determined in one case. Most solid types were DLBL or FL, while MCL was of the disseminated type. Immunohistochemistry showed all but each 2 cases of ALCL and HD were of B lineage. Follow-up of 26 patients indicated that all but one patient with primary lymphoma were still alive (range, 1-89 months) and 8 of 15 patients with secondary lymphomas died due to the progression of malignant lymphoma; the survival rate at 2 years was 50% in these patients. No elevation of anti-HTLV-I antibody was found. In situ hybridization for Epstein-Barr virus (EBV) showed no reactivity of lymphoma cells, although a few small lymphocytes were positive for EBV. Hepatitis C virus was observed in 6 of 20 (30%) patients examined and 4 of 11 (36%) cases of primary splenic lymphoma. Our findings indicate that patients with primary splenic lymphoma have a favorable prognosis after splenectomy.     

Patients With Malignant Lymphoma and HIV Infection Experiencing Remission After First-Line Treatment Have an Excellent Prognosis

BackgroundMalignant lymphoma is still the leading cause of death among AIDS-related diseases.Patients and MethodsWe performed a retrospective analysis of 50 HIV-positive lymphoma patients. The median interval between HIV and malignant lymphoma diagnosis was 4 years. Eight patients (16%) had Hodgkin lymphoma and 42 (84%) non-Hodgkin lymphoma. Among non-Hodgkin lymphoma patients, diffuse large B-cell lymphoma (n = 18, 42%), Burkitt lymphoma (n = 11, 26%), and plasmoblastic lymphoma (n = 5, 12%) were the most frequent entities.ResultsLymphoma was treated according to standard protocols. Forty-four patients (88%) received combination antiretroviral therapy, 2 (4%) were not treated, and in 4 (8%) the HIV treatment status was not clarified. Response to first-line therapy was complete response (CR) in 24 (56%), partial response (PR) in 15 (35%), and stable disease in 1 (2%). Three patients (7%) developed progressive disease, and 9 (18%) experienced relapse after CR or PR. At a median observation period of 31 (range, 0.4-192) months, the 1-, 2-, and 5-year overall survival was 87%, 79%, and 76%, respectively. At univariate analysis, remission status after first-line treatment was predictive of outcome, as the 2-year overall survival was 95%, 66%, and 0 for patients with CR, with PR, and with progressive disease (P < .001). Results of the multivariate analysis revealed lactate dehydrogenase concentration at lymphoma diagnosis (P = .046) and relapse (P = .050) to be independent factors for overall survival.ConclusionFirst-line treatment of lymphoma in HIV positive patients is crucial. Patients who experienced and maintained a first CR had a favorable prognosis.     

c-myc gene mutation in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma

The c-myc gene is involved in important cellular processes, including cell proliferation, differentiation, and apoptosis. We analyzed mutation of the c-myc gene in 51 patients with gastric lymphoma [27 patients with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 11 with high-grade MALT lymphoma, and 13 with diffuse large B-cell lymphoma (DLL)], by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. We also evaluated the relationship between mutation of the c-myc gene and regression of low-grade MALT lymphoma after Helicobacter pylori (H. pylori) eradication. Mutation in exon 2 of the c-myc gene was present in 2 of 20 (10%) patients with low-grade MALT lymphoma, in 1 of 7 (14%) patients with high-grade MALT lymphoma, and none of 10 patients with DLL. The 3 patients who had mutations of the gene, showed different patterns of mobility shift, suggesting different mutations. In addition, 15 patients with low-grade MALT lymphoma received anti-H. pylori therapy. All the patients achieved eradication. Nine of the 15 (60%) patients with low-grade MALT lymphoma showed complete regression (CR), 3 (20%) showed partial regression (PR), and 3 (20%) showed no change (NC). One of the 9 (11%) CR patients had a mutation of the c-myc gene. None of the 3 PR and 3 NC patients had mutation of the gene. There was no significant difference between the frequencies among the c-myc gene mutation in CR, in PR and in NC patients. These data suggest that mutation of the c-myc gene may not be commonly associated with development of gastric MALT lymphoma and DLL, and may not be associated with regression of low-grade MALT lymphoma after H. pylori eradication.