早期胃黏膜相关淋巴组织淋巴瘤患者52例的临床分析

目的 探讨早期胃黏膜相关淋巴组织（MALT）淋巴瘤患者的临床特点及抗幽门螺旋杆菌（Hp）治疗和抗肿瘤治疗的疗效。方法 收集2003年4月至2013年5月在天津医科大学附属肿瘤医院确诊并治疗的早期胃MALT淋巴瘤患者52例的病例资料。对Hp感染的患者进行抗Hp治疗。对抗Hp治疗失败的患者进行抗肿瘤治疗。结果 52例早期胃MALT淋巴瘤患者中,Hp感染率为88.4%。抗Hp治疗的有效率为91.3%。18例患者进行抗肿瘤治疗,有效率为66.7%。52例患者5年的总生存率为92.3%,5年无疾病进展生存率为83.1%。结论 对于早期胃MALT淋巴瘤患者,抗Hp治疗是合理和有效的治疗方法。抗Hp治疗失败的患者应进行抗肿瘤治疗,从而使患者得到长久的获益。     

原发性胃淋巴瘤临床病理和内镜特点分析

目的探讨原发性胃淋巴瘤（PGL）的临床病理和内镜下表现,提高对PGL的认识。方法对我院1999年1月～2010年3月经内镜检查、组织病理和免疫组化确诊的42例PGL的临床资料并进行分析。结果42例患者从发病到就诊时间平均5.2个月。首发症状为上腹部疼痛,依次有腹部饱胀、食欲减退、呕血与黑便、贫血、消瘦等临床表现。内镜下形态表现分弥散浸润型（17例）、多发溃疡型（14例）和隆起糜烂型（11例）。多部位、多种形态且病变范围广为其特征。内镜下常误诊为胃癌、溃疡等,需经病理学、免疫组化检查确诊。本组38例（90.5%）幽门螺杆菌（Hp）阳性。结论PGL起病较隐匿、病程较长。症状、体征不具特异性。内镜下多点深取组织活检及病理学、免疫组化检查是提高PGL确诊率和早期诊断率的重要方法。Hp感染与PGL有密切相关性。     

Guidelines for the management of diffuse large B‐cell lymphoma

Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8–10 months. We conducted a phase II trial of standard CHOP‐21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2–6: 1000 mg day 1) (CHOP‐O) followed by 12 months ofatumumab maintenance (1000 mg given 8‐weekly for up to six cycles). Forty‐three patients were recruited of whom 37 were evaluable. Seventy‐three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide‐based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression‐free survival was 6·2 months (95% confidence interval [CI] 4·9–14·0 months) and median OS was 11·4 months (95% CI 6·4–25·6 months). Treatment‐naïve and TP53‐intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non‐neutropenic infections were observed. There were no treatment‐related deaths. Seven patients received platinum‐containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP‐O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed.     

Clinical activity of everolimus in relapsed/refractory marginal zone B‐cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group

The International Extranodal Lymphoma Study Group coordinated a phase II trial to evaluate the activity and safety of everolimus in marginal zone lymphomas (MZLs). Thirty patients with relapsed/refractory MZLs received everolimus for six cycles or until dose‐limiting toxicity or progression. Median age was 71 years (range, 51–88 years). Twenty patients had extranodal, six splenic, four nodal MZL. Twenty‐four patients had stage III–IV. Median number of prior therapies was two (range 1–5). Seventeen patients had early treatment discontinuation, in most cases due to toxicity. Median number of cycles was 4·5 (range, 1–16). Among the 24 assessable patients, the overall response rate (ORR) was 25% (95% confidence interval: 10–47). Grade 3–4 adverse events were neutropenia and thrombocytopenia (17% of patients, each), infections (17%), mucositis and odontogenic infections (13%) and lung toxicity (3%). The median response duration was 6·8 months (range, 1·4–11·1+). After a median follow‐up of 14·5 months, five deaths were reported: four deaths were due to lymphoma, one was due to toxicity. In an intent‐to‐treat analysis, the projected median progression‐free survival was 14 months. The moderate antitumour activity of everolimus in relapsed/refractory MZLs and the observed toxicity limit its therapeutical applicability in these indolent entities. Lower doses of the drug and, perhaps, different strategies including combination with additional agents need to be explored.     

Regression of gastric T cell lymphoma with eradication of Helicobacter pylori

Helicobacter pylori is thought to be important in the pathogenesis of chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric B cell lymphoma of mucosa associated lymphoid tissue. The mechanism of evolution from chronic gastritis to monoclonal B cell proliferation is not known but is thought to be dependent on antigen specific T cells to H pylori and its products. Here, we report a case of gastric T cell lymphoma associated with chronic H pylori gastritis which regressed with eradication of the organism. This is the first report of a gastric T cell lymphoma regressing with H pylori eradication, and suggests a causal link between primary gastric T cell lymphoma and this organism.     

幽门螺杆菌阴性早期胃癌的内镜及组织学特点分析

目的:分析并总结幽门螺杆菌( Helicobacter pylori, HP)阴性早期胃癌或高级别上皮内瘤变的内镜及组织学特点。 方法:检索在解放军总医院第七医学中心2013年1月—2020年1月诊断为早期胃癌或高级别上皮内瘤变的患者,按照 HP阴性胃癌诊断标准纳入病例,回顾性分析其临...     

Use of rituximab in diffuse large B-cell lymphoma in the salvage setting

The addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was a milestone in the development of front-line therapy for diffuse large B-cell lymphoma (DLBCL). R-CHOP and equivalent rituximab-containing anthracycline-based regimens are now widely accepted as the standard of care in this setting. However, the optimal treatment for patients with DLBCL relapsing or progressing after front-line therapy is not yet established. This review explores the role of rituximab in the treatment of DLBCL in the salvage setting, as monotherapy, in combination with chemotherapy or novel agents, and in the context of autologous stem cell transplantation (ASCT). Current evidence suggests that rituximab may improve outcomes in several ways: the higher response rates achieved with rituximab-based induction in the salvage setting optimize the number of patients who are able to proceed to high-dose therapy -ASCT; rituximab may improve outcomes following ASCT when used as post-transplantation consolidation/maintenance therapy; and addition of rituximab to salvage regimens may improve outcomes for patients ineligible for transplantation. However, patients refractory to or relapsing after first-line therapy (including rituximab-based regimens) still have a poor prognosis. In conclusion, rituximab in salvage therapy for DLBCL is effective and well tolerated. Ongoing studies will further clarify the optimal use of rituximab in the salvage setting.     

Secondary non-Hodgkin lymphoma (NHL) in children and adolescents after childhood cancer other than NHL

The emergence of non-Hodgkin lymphoma (NHL) during childhood and adolescence as a secondary neoplasm (SN) after previous cancer other than NHL is rare. To describe the characteristics and outcome of NHL following previous cancer other than NHL in children and adolescents, this study analysed the data of patients reported to the NHL-Berlin-Frankfurt-Münster study centre from 1986 to 2005. Out of the total of 2968 NHL-patients registered, 11 patients were assessed as having suffered from NHL as a proven SN. Four additional children had most likely suffered from NHL as an SN, but a late relapse of the first neoplasm could not be ruled out unequivocally. In the patients with proven SN, median age at diagnosis of the primary malignancy was 3.9 years (range 2-11.7). The median age at diagnosis of NHL was 7.6 years (range 4.7-18). Only lymphoblastic (n = 7) and diffuse large B-cell (n = 4) lymphomas were diagnosed as SN. The estimated 5-year event-free survival from time of diagnosis of NHL was 91% [95% confidence interval (CI) 74-100%] in patients with proven SNs and 84% (95% CI 63-100%) when the patients with probable SNs were included in the analysis. We concluded that secondary NHL in children and adolescents confers a favourable prognosis.     

筛查幽门螺杆菌感染预防胃癌的费用效果分析

目的评价在人群中筛选幽门螺杆菌感染以预防胃癌的临床和经济学效果.方法用Markov模型估计在10万名40岁～45岁人群中筛查幽门螺杆菌感染者并对筛查试验阳性者进行治疗的远期效果及费用,并与不进行任何干预的结果相比较,进行卫生经济学评价.对治疗感染者减少胃癌发生危险度的有效率和胃癌发病率进行敏感性分析.结果在有效率为50%时,每筛查10万人可减少291例胃癌的发生,增加2612个生命年.当预防胃癌的有效率从5%到100%变化时,每增加一个生命年的费用从7747元下降到2325元,在胃癌高发区筛查更经济有效.结论筛查幽门螺杆菌感染是一种潜在的能减少胃癌发生的有效措施.     

Front‐line management of indolent non‐Hodgkin lymphoma in Australia. Part 2: mantle cell lymphoma and marginal zone lymphoma

Mantle cell lymphoma (MCL) and the marginal zone lymphoma (MZL) subtypes (nodal MZL, extra‐nodal MZL of mucosa‐associated lymphoid tissue (MALT lymphoma) and splenic MZL) are uncommon lymphoma subtypes, accounting for less than 5–10% of all non‐Hodgkin lymphoma. The evidence base for therapy is therefore limited and enrolment into clinical trials is preferred. Outcomes for patients with MCL have been steadily improving mainly due to the adoption of more intense strategies in younger patients, the use of rituximab maintenance and the recent introduction of bendamustine in older patients. MZL is a more heterogeneous group of cancer with both nodal, extra‐nodal and splenic subtypes. Extranodal MZL may be associated with autoimmune or infectious aetiologies, and can respond to eradication of the causative pathogen. Proton pump inhibitor plus dual antibiotics in Helicobacter pylori positive gastric MALT lymphoma is curative in many patients. Watchful waiting is appropriate in most patients with asymptomatic advanced stage disease, which tends to behave in a particularly indolent manner. Other options for symptomatic disease include splenectomy, chemoimmunotherapy with rituximab and, more recently, targeted therapies.     

Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study

High cure rates are possible in children with localized mature B-cell lymphoma (B NHL) using a variety of chemotherapeutic strategies. To reduce late sequelae, the duration and intensity of chemotherapy has been progressively reduced. The Lymphome Malins de Burkitt (LMB) 89 study reported long-term survival in almost all children with localized resected disease treated with two courses of COPAD (cyclophosphamide, vincristine, prednisolone and doxorubicin). This study was designed to confirm the effectiveness of this approach in a larger number of patients in a multinational co-operative study. The patient cohort was part of an international study (French-American-British LMB 96), which included all disease stages and involved three national groups. Patients in this part of the study had resected stage I or completely resected abdominal stage II disease. Following surgery, two courses of COPAD were given, without intrathecal (IT) chemotherapy. One hundred and thirty-two children were evaluable. Two of 264 (0.9%) courses were associated with grade IV toxicity (one stomatitis and one infection). With a median follow up of 50.5 months, the 4 year event-free survival is 98.3% and overall survival is 99.2%. Children with resected localized B-NHL can be cured with minimal toxicity following two courses of low intensity treatment without IT chemotherapy.     

Male gender is an adverse prognostic factor in B-cell lymphoma patients treated with immunochemotherapy

Male gender is an adverse prognostic factor in Hodgkin's lymphoma, but no such association has yet been established in non-Hodgkin lymphomas. Here, we have evaluated whether gender has prognostic impact on the survival of patients with B-cell non-Hodgkin lymphoma in the postrituximab era of lymphoma therapies. The study populations consisted of 217 diffuse large B-cell lymphoma (DLBCL) and 110 follicular lymphoma (FL) patients treated with immunochemotherapy. Hundred and sixty chemotherapy-treated DLBCL patients served as a control group. According to Kaplan-Meier analyses, female patients had a significantly better progression-free survival than men both in DLBCL (4 yr PFS 75% vs. 60%; P= 0.013) and in FL (4 yr PFS 68% vs. 52%, P=0.036) patients treated with immunochemotherapy. In chemotherapy-treated DLBCL patients, no difference in survival between the genders was found. The results support the idea that women seem to respond better to rituximab.     

The impact of hepatitis B virus infection and vaccination on the development of non‐Hodgkin lymphoma

Hepatitis B virus (HBV) infection has been documented as a risk factor for non‐Hodgkin lymphoma (NHL). However, there are few large cohort studies, and there is no report about the impact of HBV vaccination. We conducted this study to evaluate these issues. We used the nationwide cohort of the Taiwan National Health Insurance Research Database for 1997–2013. We compared the incidence and the risk of developing NHL and CD20⁺ aggressive lymphoma between HBV and non‐HBV cohorts. The hazard ratios (HRs) were computed using Cox proportional hazards models. We matched these two large cohorts to reconfirm the data. We also compared the incidence of NHL between cohorts born before and after the inception of universal HBV vaccination. We found that HBV infection increased the risk for developing NHL and CD20⁺ aggressive lymphoma, with HRs of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person‐years, respectively, compared to the non‐HBV cohort. The incidence of NHL in the cohort born in the era before universal HBV vaccination was higher with 1.85 per 100 000 person‐years compared to 0.74 in the cohort born later aged younger than 20. Our study confirms that HBV confers a greater risk for developing NHL, especially CD20⁺ aggressive lymphoma. The impact of HBV vaccination is protective against lymphoma development in the teenagers in an endemic area, but longer follow‐up is needed for older age.     

Long‐term treatment of localized gastric marginal zone B‐cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancer

Background and Aim: According to a few recent reports on the long‐term clinical outcome of gastric marginal zone B‐cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long‐term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer. Methods: Between April 1996 and May 2008, 60 patients (31 men and 29 women; mean age 58.1 years) with localized gastric MALT lymphoma (stage I and II¹ according to Lugano classification) were analyzed retrospectively. Results: Forty‐eight patients (82.6%) achieved complete remission by eradication therapy. Radiation therapy was conducted on eight patients as second‐line treatment, and all of them achieved remission. The median follow‐up period was 76 months (range, 12–157 months). One patient had local relapse after remission for 5 years and three patients developed early gastric cancer without recurrence of lymphoma (5%). All of the three gastric cancers appeared in the same areas where MALT lymphoma had been eradicated. Conclusion: Eradication therapy and radiation therapy for localized gastric MALT lymphoma have a favorable long‐term outcome, though regular follow‐up endoscopy should be performed for detecting metachronous early gastric cancer.     

胃黏膜相关淋巴组织淋巴瘤临床研究及随访

目的探讨胃黏膜相关淋巴组织淋巴瘤的临床特征及治疗策略。方法采用回顾性方法对32例经组织学确诊的胃黏膜相关淋巴组织淋巴瘤进行随访。结果32例患者中多数起病隐匿，上腹痛为主要症状，也有以消化道出血入院者。内镜下病变主要分布在胃窦部，以隆起型和溃疡型表现为主。首次胃镜检查约25％获正确诊断。本组病例幽门螺杆菌感染率约为88％。20例（62．5％）接受了手术治疗，15例（46．88％）行幽门螺杆菌根除治疗，其中，3例早期阶段患者获得组织学完全缓解。结论胃黏膜相关淋巴组织淋巴瘤的临床表现、内镜下特征和病理特点的认识有待进一步提高。对早期阶段患者幽门螺杆菌治疗当属首选。     

Overall survival of children and adolescents with mature B cell non‐Hodgkin lymphoma who had refractory or relapsed disease during or after treatment with FAB/LMB 96: A report from the FAB/LMB 96 study group

We determined the risk factors associated with poor survival in children and adolescents with de novo mature B cell non‐Hodgkin lymphoma (B‐NHL) who had refractory or relapsed disease during or after the French‐American‐British mature lymphoma B (FAB/LMB) 96 multi‐agent chemotherapy. Among the 1 111 registered on study, 104 patients (9·4%) had refractory disease or disease relapse after first complete remission. Among these 104 patients, 28 (27%) patients had refractory disease and 76 (73%) had relapsed disease. The estimated 1‐ and 2‐year overall survival (OS) (95% confidence interval) was 31·5% (23·3–41·0%) and 22·3% (15·3–31·4%), respectively. Prognostic analysis of OS using a Cox multivariate model showed that factors independently associated with OS included lactate dehydrogenase ≥2 upper normal limit [hazard ratio (HR) = 2·86 (1·57–5·2), P = 0·0006]; time to failure (>6 months) [HR = 0·59 (0·36–0·97), P = 0·038]; and failure in bone marrow [HR = 2·78 (1·65–4·68), P = 0·0001]. New therapeutic strategies are required to significantly reduce refractory disease and disease relapse in patients with newly diagnosed mature B‐NHL and, more importantly, there is a critical need to develop novel retrieval approaches in patients with chemotherapy‐resistant disease.     

Prospective subgroup analyses of the randomized MCL‐002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma

In the mantle cell lymphoma (MCL)‐002 study, lenalidomide demonstrated significantly improved median progression‐free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long‐term follow‐up data and results of preplanned subgroup exploratory analyses from MCL‐002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL‐002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1–21; 28‐day cycles) or single‐agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent‐to‐treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single‐agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history.     

Primary lymphomas in the gastrointestinal tract

Primary gastrointestinal (GI) lymphomas are uncommon diseases that can involve the whole GI tract. The etiologies of the disease remain unclear, and potential risk factors include celiac disease, Helicobacter pylori infection, use of immunosuppressive agents, human immunodeficiency virus (HIV) or Epstein–Barr virus (EBV) infection and inflammatory bowel disease, etc. Diffuse large B‐cell lymphoma (DLBCL) and mucosa‐associated lymphoid tissue (MALT) lymphoma are the most common subtypes of GI lymphomas. B‐cell lymphomas of the GI tract are more common in Western countries, while in Asia–Pacific region T‐cell lymphomas are more frequently reported. In this review, lymphomas in the esophagus, stomach and intestine are described, including their epidemiology, histology, clinical manifestations, endoscopic findings, radiological features and treatment.     

Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: A comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.