VEGF、p53在非霍奇金淋巴瘤患者血清中的表达及其临床意义的研究

目的:探讨VEGF、p53在非霍奇金淋巴瘤(NHL)的微转移检测及治疗等方面的作用。方法:ELISA法检测60例非霍奇金淋巴瘤患者血清VEGF及p53的含量,用50例健康人血清作对照。结果:NHL患者血清VEGF及p53浓度的平均数较健康对照者的明显增高(t=8.23,P<0.001;t=5.141,P<0.001);合并白血病或骨髓浸润的NHL患者的VEGF及p53水平明显高于未有骨髓浸润者;临床治疗有效的患者,治疗后VEGF及p53浓度的平均数较治疗前均有明显下降;VEGF及p53表达水平与患者年龄和性别均无相关性;而惰性淋巴瘤的VEGF、p53水平比侵袭性和高侵袭性的淋巴瘤水平低(P<0.05);Ⅰ、Ⅱ期和Ⅲ、Ⅳ期患者VEGF、p53表达水平差异有统计学意义(P<0.05)。结论:VEGF、p53在NHL患者血清中的表达,对临床分期、病理恶性程度、肿瘤侵犯程度有一定指导意义;VEGF、p53的检测对NHL治疗反应的判断有一定价值,有望成为判断NHL预后的新指标。     

VEGF、p53在非霍奇金淋巴瘤患者血清中的表达及其临床意义的研究

目的：探讨VEGF、p53在非霍奇金淋巴瘤（NHL）的微转移检测及治疗等方面的作用。方法：ELISA法检测60例非霍奇金淋巴瘤患者血清VEGF及p53的含量,用50例健康人血清作对照。结果：NHL患者血清VEGF及p53浓度的平均数较健康对照者的明显增高（t=8.23,P〈0.001;t=5.141,P〈0.001）;合并白血病或骨髓浸润的NHL患者的VEGF及p53水平明显高于未有骨髓浸润者;临床治疗有效的患者,治疗后VEGF及p53浓度的平均数较治疗前均有明显下降;VEGF及p53表达水平与患者年龄和性别均无相关性;而惰性淋巴瘤的VEGF、p53水平比侵袭性和高侵袭性的淋巴瘤水平低（P〈0.05）;Ⅰ、Ⅱ期和Ⅲ、Ⅳ期患者VEGF、p53表达水平差异有统计学意义（P〈0.05）。结论：VEGF、p53在NHL患者血清中的表达,对临床分期、病理恶性程度、肿瘤侵犯程度有一定指导意义;VEGF、p53的检测对NHL治疗反应的判断有一定价值,有望成为判断NHL预后的新指标。     

Place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens

The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.     

原发性睾丸非霍奇金淋巴瘤1例合并文献分析

目的提高对原发性睾丸非霍奇金淋巴瘤(PTL)的全面认识,从而选择更合适的治疗方法,提高患者生存率。方法回顾性分析1例经病理活检证实为原发性睾丸非霍奇金淋巴瘤的临床资料,并结合文献进行分析。结果 PTL患者对R-CHOP方案耐受性较好,需继续观察追踪治疗效果。结论原发性睾丸非霍奇金淋巴瘤较为罕见,有明显的结外侵犯趋势,预后较差。对PTL R-CHOP方案是较佳的选择,治疗疗效尚需大样本的临床试验进一步确定。     

Use of rituximab in three children with relapsed/refractory Burkitt lymphoma

Monoclonal antibodies have provided new promise for patients with B-cell malignancies. Rituximab is a monoclonal antibody against B-lymphocytes that express CD20; it is used for the treatment of patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Very few data are available regarding the treatment of children with non-Hodgkin lymphoma with rituximab. In this article, we reported three children with primary refractory/relapsed B-cell-non-Hodgkin lymphoma, who were successfully treated with a combination of intensive chemotherapy protocol plus rituximab. In all three of our cases, the patients are still in complete remission. Our aim is to emphasize the importance of use of rituximab in the treatment of childhood B-cell non-Hodgkin lymphoma.     

The Management of Children with Lymphomas

Lymphomas account for 10–15% of all paediatric malignancies. They are highly curable with 5 year survival rates of up to 95% for Hodgkin lymphoma and 82% for non-Hodgkin lymphoma. These excellent results have focused recent attention on reducing the burden of treatment-related morbidity while maintaining the excellent outcomes. Lymphomas are highly radiosensitive and radiotherapy was used historically in the treatment of both paediatric Hodgkin and non-Hodgkin lymphomas. As the late effects of radiotherapy, including second tumours, were recognised, successive protocols seeking to minimise late effects were developed that reduced the use of radiotherapy. Current treatment protocols for non-Hodgkin lymphoma are chemotherapy based and radiotherapy has been virtually eliminated. In contrast, current paediatric Hodgkin lymphoma protocols continue to use radiotherapy as part of combined modality treatment, targeted according to risk factors and response and at the minimum effective dose. This article reviews the treatment of Hodgkin lymphoma in children with particular emphasis on the role of radiotherapy.     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤的临床分析

目的 观察利妥昔单抗联合CHOP方案治疗CD20阳性B细胞非霍奇金淋巴瘤的临床疗效及毒副反应.方法 8例B细胞非霍奇金淋巴瘤均采用利妥昔单抗联合化疗,利妥昔单抗375 ms/m2于每1周期化疗前1天静脉滴注,每3周为1疗程,4～6周期后评价疗效及毒副反应.结果 8例患者中,CR 7例,PR 1例,总有效率100%.主要...     

Bone marrow transplantation for lymphoma CR1

PURPOSE OF REVIEW: Despite several reports showing the superiority of autologous stem cell transplantation over conventional chemotherapy in the salvage treatment of non-Hodgkin lymphoma, its use as part of first-line therapy in this disease is still controversial. The review highlights the most relevant studies on autologous stem cell transplantation for non-Hodgkin lymphoma at diagnosis published over the past year. RECENT FINDINGS: Several recent studies have shown that autologous stem cell transplantation may offer survival benefits in patients with both diffuse large cell lymphoma and follicular cell lymphoma whose prognostic features are poor. An advantage of autologous stem cell transplantation has also been documented for other non-Hodgkin lymphoma subtypes, in particular mantle-cell lymphoma, in which autologous stem cell transplantation is probably the most effective first-line option presently available. Nevertheless, whether autologous stem cell transplantation is definitely better than conventional chemotherapy is still under discussion, and the issue is still less clear, given the new opportunities offered by rituximab combined with chemotherapy. Autologous stem cell transplantation may also benefit from the addition of rituximab as an in vivo purging agent. Thus, large randomized trials are required to fully define the role of autologous stem cell transplantation in first-line treatment for high-risk non-Hodgkin lymphoma. Such trials should compare autologous stem cell transplantation with chemotherapy, both supplemented with rituximab, in the most frequent CD20+ lymphoma subtypes. The up-front use of autologous stem cell transplantation might find support from the recent observation that patients who do not respond to this treatment may still have a good chance of being rescued by reduced-intensity allogeneic transplantation. SUMMARY: Autologous stem cell transplantation remains a valid research strategy in first-line therapy and, along with new agents and nonmyeloablative allogeneic transplantation, may help to increase the cure rate for high-risk non-Hodgkin lymphoma.     

P-糖蛋白在非霍奇金淋巴瘤组织中的表达及意义

目的探讨非霍奇金淋巴瘤组织中P-gp(P-糖蛋白)的表达及临床意义。方法应用免疫组化法检测117例非霍奇金淋巴瘤组织中P-gp的表达及其与生存率的关系。结果初治组P-gp表达的阳性率为30.26%(23/76);复发/难治组阳性率高达68.29%(28/41),2组差异有统计学意义(P﹤0.05)。P-gp表达阳性者化疗后生存时间明显低于阴性表达者,与预后显著相关(P<0.01)。结论 P-gp在非霍奇金淋巴瘤组织中高表达是多药耐药产生的基础,动态监测P-gp能指导临床治疗及预后。     

侵袭性T细胞非霍奇金淋巴瘤的化疗

T细胞非霍奇金淋巴瘤是一组具有独特临床和病理特征的疾病,与B细胞淋巴瘤相比,侵袭性更强,化疗敏感性差。为探索有效的治疗方案,近年来,新的药物如吉西他滨、靶向药物联合化疗及高剂量化疗联合造血干细胞移植被研究用于治疗T细胞淋巴瘤,并取得了一些进展。     

Autologous hematopoietic stem cell transplant in first remission in non-Hodgkin’s lymphoma

The PARMA trial clarified the role of hematopoietic stem cell transplant in patients with non-Hodgkin’s lymphoma in chemotherapy-sensitive relapse. With the goal of improving overall response and survival rates, hematopoietic stem cell transplant has been incorporated into the front-line treatment plan in some studies. While multiple clinical trials have been designed to address this issue, they have varied in their treatment regimens, patient populations and outcomes. This review will summarize and analyze the data obtained so far and provide practitioners with recommendations for the application of high-dose chemotherapy and hematopoietic stem cell transplant as part of the initial treatment of patients with both indolent and aggressive non-Hodgkin’s lymphoma. Based upon the current literature, hematopoietic stem cell transplant cannot be recommended as first-line therapy in patients with non-Hodgkin’s lymphoma outside the setting of a clinical trial.     

Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.     

Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy

Microsatellite instability (MSI) in haematopoietic malignancies has been controversial. Particularly in non-Hodgkin lymphoma, the data published to date lack unity. Using a unique fluorescent technique, we found MSI in eight (14%) tumours in a panel of 59 carefully selected non-Hodgkin lymphoma patients. Our fluorescent technique also reveals two qualitatively distinct modes of MSI, i.e. Type A and Type B. Based on our previous studies using DNA mismatch repair (MMR) gene-knock out animals, we have concluded that Type A MSI is a direct consequence of defective MMR. MSI observed in non-Hodgkin lymphomas was uniformly Type A, which implies that MMR deficiency occurs in this malignancy. Intriguingly, in non-Hodgkin lymphoma patients treated by CHOP/VEPA-based therapies, response to chemotherapy was significantly worse in those with microsatellite-unstable tumours (p = 0.027). As a consequence, the patient outcomes at 1 year after treatment were significantly less favourable in this population (p = 0.046), although the survival difference was not statistically confirmed in a longer term. These findings suggest that in some non-Hodgkin lymphomas MMR deficiency may lead to drug resistance in tumour cells and, consequently, to poor patient outcomes. In non-Hodgkin lymphoma, MSI may be a potential biomarker that predicts the tumour response against chemotherapy.     

Primary non-Hodgkin's lymphoma of the gall bladder.

Primary non-Hodgkin lymphoma of the gallbladder is a very rare location of extranodal non-Hodgkin lymphomas. A patient with a primary non-Hodgkin lymphoma of the gallbladder is reported and in addition, the English literature is reviewed. Clinical presentation, diagnostic evaluation, histopathologic findings, treatment modalities and prognosis of primary gallbladder lymphomas reported up to date are reviewed and discussed. Our patient was diagnosed as a T-cell lymphoblastic lymphoma, after cholecystectomy, and had no evidence of disease elsewhere. She was treated with combination chemotherapy and complete remission was achieved. She remains free of disease 9 years later. Review of the literature over a 30-year period revealed only 12 cases of well-documented primary non-Hodgkin lymphoma involvement of the gallbladder, including the present case. Patients present clinically with symptoms and signs indicating either biliary tract pathology or a gastrointestinal tumor. Diagnostic investigation included ultrasound of the upper abdomen, computed tomography of the abdomen and pelvis, oral cholecystography, percutaneous cholangiography and endoscopic retrograde cholangiopangreatography. Preoperative diagnosis was established in none of the patients. Treatment modalities included surgery and postoperative chemotherapy and irradiation. The prognosis is overall poor and only 2 patients are alive after 1 and 9 years respectively, the latter being our case. Here we document the first reported case of a patient with primary T-cell lymphoblastic non-Hodgkin lymphoma of the gallbladder. Review of the literature shows the existence of non-Hodgkin lymphoma of the gallbladder, its rarity and its general dismal prognosis.     

Primary Non-Hodgkin's Lymphoma of the Gall Bladder

Primary non-Hodgkin lymphoma of the gallbladder is a very rare location of extranodal non-Hodgkin lymphomas. A patient with a primary non-Hodgkin lymphoma of the gallbladder is reported and in addition, the English literature is reviewed. Clinical presentation, diagnostic evaluation, histopathologic findings, treatment modalities and prognosis of primary gallbladder lymphomas reported up to date are reviewed and discussed. Our patient was diagnosed as a T-cell lymphoblastic lymphoma, after cholecystectomy, and had no evidence of disease elsewhere. She was treated with combination chemotherapy and complete remission was achieved. She remains free of disease 9 years later. Review of the literature over a 30-year period revealed only 12 cases of well-documented primary non-Hodgkin lymphoma involvement of the gallbladder, including the present case. Patients present clinically with symptoms and signs indicating either biliary tract pathology or a gastrointestinal tumor. Diagnostic investigation included ultrasound of the upper abdomen, computed tomography of the abdomen and pelvis, oral cholecystography, percutaneous cholangiography and endoscopic retrograde cholangiopangreatography. Preoperative diagnosis was established in none of the patients. Treatment modalities included surgery and postoperative chemotherapy and irradiation. The prognosis is overall poor and only 2 patients are alive after 1 and 9 years respectively, the latter being our case.Here we document the first reported case of a patient with primary T-cell lymphoblastic non-Hodgkin lymphoma of the gallbladder. Review of the literature shows the existence of non-Hodgkin lymphoma of the gallbladder, its rarity and its general dismal prognosis.     

Use of bortezomib in B-cell non-Hodgkin’s lymphoma

The ubiquitin–proteasome pathway plays a critical role in the regulated degradation of proteins involved in cell cycle control and tumor growth. Bortezomib (Velcade^®, formerly known as PS-341) is a potent proteasome inhibitor. In preclinical studies, bortezomib has demonstrated activity against a variety of B-cell malignancies by inducing apoptosis and sensitizing tumor cells to radiation or chemotherapy. Based on these findings, clinical trials have been conducted with bortezomib in B-cell non-Hodgkin’s lymphoma. In these studies, bortezomib was generally well tolerated with manageable toxicities and showed promising clinical activity. Mantle cell lymphoma was significantly more sensitive to bortezomib than other non-Hodgkin’s lymphomas. Bortezomib may have far-reaching potential in the treatment of B-cell non-Hodgkin’s lymphoma.     

Advances in the management of patients with non-Hodgkin’s lymphoma

Non-Hodgkin’s lymphoma is the fifth most common cause of death due to cancer and has been rising at a rate of 4% per year for the last four decades. Although ‘traditional’ chemotherapy and radiotherapy have had important contributions to improving outcomes, new tools in the treatment of non-Hodgkin’s lymphoma are needed. This review describes therapeutic modalities that are currently being used or are in the process of being developed and which are based on concepts divergent from ‘traditional’ approaches to managing non-Hodgkin’s lymphoma.     

Effect of cytomegalovirus prophylaxis with immunoglobulin or with antiviral drugs on post-transplant non-Hodgkin lymphoma: a multicentre retrospective analysis

BACKGROUND: Post-transplant non-Hodgkin lymphoma is a feared complication of immunosuppressive treatment and is associated with high mortality. Most post-transplant lymphomas develop from the uncontrolled proliferation of Epstein-Barr-virus (EBV)-infected B lymphocytes. No reliable methods for the prevention of EBV infection and lymphoma are available. We aimed to elucidate the effect of prophylactic treatment for cytomegalovirus (CMV) infection on the incidence of post-transplant lymphomas. METHODS: In a multicentre retrospective study, we analysed the incidence of post-transplant non-Hodgkin lymphoma in 44 828 recipients of deceased-donor kidney transplants who were reported to the scientific registry of the Collaborative Transplant Study. Patients had received antiviral drugs (aciclovir or ganciclovir) or anti-CMV immunoglobulin to prevent CMV infection according to the transplant centres' protocols, or no CMV prophylaxis. Standardised incidence ratios (SIR) of lymphoma were calculated and compared by chi(2) analyses FINDINGS: During the first post-transplantation year, 30 255 patients who did not receive CMV prophylaxis developed lymphomas at SIR 26.4. Lymphoma incidence in 12 470 patients who received antiviral treatment was nearly identical (SIR 24.2, p=0.62) to that in patients who did not receive CMV prophylaxis. However, 2103 patients who received anti-CMV immunoglobulin showed a complete absence of lymphomas in the first after-transplantation year (SIR 0; p=0.012 vs no treatment, p=0.016 vs antivirals). In the subsequent 5 years of follow-up, new cases of lymphoma developed at similar rates in all three groups (p=0.97). INTERPRETATION: These findings suggest that prophylactic anti-CMV immunoglobulin prevents the development of early post-transplant non-Hodgkin lymphoma in kidney-graft recipients. Prophylactic treatment with antiviral drugs does not reduce the risk of post-transplant lymphoma.     

Rituximab (Rituxan®/MabThera®): the first decade (1993–2003)

The first antibody approved for the treatment of cancer, rituximab (Rituxan^®/MabThera^®), underwent clinical development between 1993 and 1996. It fulfilled predictions dating back to the early 1900s regarding the therapeutic effect of antibodies and sparked a renewed interest in this area of research. Rituximab was approved, in the USA in 1997 and in Europe in 1998, for the treatment of patients with non-Hodgkin’s lymphoma. Since then, hundreds of thousands of patients have been treated with rituximab. In 2002, rituximab became the number one anticancer drug worldwide. During its first decade of use (1993–2003), rituximab has had an important impact on treatment strategies for lymphoma and other hematologic malignancies. During the 5 years following approval, its applications expanded beyond non-Hodgkin’s lymphoma to a variety of malignant and non-malignant B-cell disorders. Also, as a result of its early clinical trials, initiatives came about that eventually led to the development of the new international response criteria for non-Hodgkin’s lymphoma. Rituximab has been characterized as the most important therapeutic development of the decade.     

Lymphomes non-hodgkiniens des tissus mous maxillofaciaux : à propos de deux cas et revue de la littérature

The extranodal non-Hodgkin lymphomas of maxillofacial soft tissues are rare. We report two cases of maxillofacial soft tissue non-Hodgkin lymphoma treated with chemotherapy followed by localized radiotherapy with complete remission after 3 and 6 months. We study the clinical, radiological and histopathological features as well as the treatment and the prognosis of extranodal non-Hodgkin lymphomas maxillofacial muscles.