Rituximab在非霍奇金淋巴瘤治疗中的作用

Rituximab，又称为美罗华，是第一个由美国FAD批准用于治疗非霍奇金淋巴瘤（Non—Hodgkin’s lymphoma，NHL）的单克隆抗体。Rituximab是基因工程人鼠嵌合型单克隆抗体，是由鼠Fab和人Fc构成，分子质量约45000。可特异地与B淋巴细胞表面的CD20抗原结合，并引发一系列作用，导致B淋巴细胞的死亡。Rituximab，不但可用于NHL的治疗，还可用于特发性血小板减少性紫癜、多发性骨髓瘤、慢性淋巴细胞白血病等多种免疫相关性疾病的治疗。现就Rituximab在NHL治疗中的作用作一综述。     

美罗华联合化疗对非霍奇金淋巴瘤疗效的Meta分析

目的综合评价美罗华联合化疗对非霍奇金淋巴瘤的疗效。方法应用国际Cochrance协作网的系统评价方法,对关于非霍奇金淋巴瘤接受美罗华联合化疗组与单纯化疗组疗效比较的随机和半随机试验研究的结果进行系统评价。结果共检索到6个试验包括1132例患者,美罗华联合化疗组的完全缓解率高于单纯化疗组(OR=4.15,95%CI2.36～7.30,P<0.00001),经异质性检验显示6个试验存在异质性(χ2=15.15,P=0.010)。采用随机效应模型进行综合分析。敏感性分析亦证实美罗华联合化疗的疗效优于单纯化疗组(OR=5.14,95%CI3.38～7.81,P<0.00001)。结论美罗华联合化疗对非霍奇金淋巴瘤有一定疗效,有必要开展更多设计良好的临床随机对照试验,进一步证明其临床效果。     

Regression of pulmonary MALT lymphoma after treatment with rituximab

We describe a patient with extranodal (pulmonary) marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) who was refractory to treatment with cytotoxic chemotherapy. After a single four-week course of rituximab she had significant regression of pulmonary lesions and remains progression free 19 months after finishing her treatment. This case report demonstrates the potential efficacy of rituximab as a single therapeutic agent in patients with pulmonary MALT lymphoma.     

Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy

A 16-year-old patient with steroid-dependent nephrotic syndrome with more than 35 relapses developed severe relapsing idiopathic thrombocytopenic purpura (ITP). At the age of 2 years, nephrotic syndrome was diagnosed and successfully treated with a standard prednisone regimen. Frequent relapses occurred. Treatment with oral cyclophosphamide followed by cyclosporine was successful, but several attempts to withdraw steroids failed and the patient suffered from multiple relapses. At the age of 12 years, renal biopsy revealed focal segmental glomerulosclerosis and cyclosporine toxicity. A second course of oral cyclophosphamide was unsuccessful and tacrolimus resulted in the development of diabetes mellitus, which was reversed after discontinuation of the drug. At the age of 15 years the patient, still being steroid dependent, developed ITP. Neither steroids nor intravenous immunoglobulins induced permanent remission. Only weekly immunoglobulin infusions could temporarily restore the platelet count. To treat ITP in this desperate situation we decided to deplete B-cells with the monoclonal anti-CD20 antibody rituximab. Intravenous infusions of rituximab (375 mg/m²) were given once weekly for 4 consecutive weeks without adverse events. Four weeks after the first rituximab dosage, the thrombocyte count increased to normal values. There has been no subsequent relapse of either thrombocytopenia or nephrotic syndrome (on cyclosporine, without steroids) to date. We conclude that B-cell depletion with rituximab might have altered the course of steroid-dependent nephrotic syndrome in our patient.     

Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study

Rituximab is a chimeric monoclonal antibody that binds specifically to the CD20 antigen expressed in most B cell lymphomas. As single agent or in combination with chemotherapy rituximab has shown significant activity in patients with relapsing or refractory aggressive lymphomas. Because T cell rich B cell lymphomas (TCRBCL) also express the CD20 antigen, we decided to evaluate the efficacy and tolerability of the anti-CD20 monoclonal antibody rituximab combined with chemotherapy in four patients with either primary refractory or early relapsed TCRBCL. The chemotherapy regiment consisted of vinorelbin and gemcitabine, a combination with known efficacy in patients with refractory aggressive lymphomas. The patients received 6 cycles of rituximab at the dose of 375 mg/m², combined with vinorelbine 25 mg/m² and gemcitabine 800 mg/m² at 3-week intervals. Three complete responses and one partial response were observed among our four patients with refractory or early relapsed TCRBCL without significant adverse effects, indicating considerable efficacy of this combination. Therefore, rituximab should be tested in combination with chemotherapy in the front line treatment of patients with TCRBCL.     

Rituximab therapy in Waldenstrom's macroglobulinemia: Preliminary evidence of clinical activity

To assess the preliminary efficacy of rituximab therapy in Waldenstrom's macroglobulinemia (WM), we examined the clinical and laboratory data for all patients with WM treated on IDEC Pharmaceuticals sponsored trials and one patient treated at Walter Reed Army Medical Center. Seven symptomatic patients with WM were treated with four (n = 6) or eight (n = 1) weekly infusions of rituximab (375 mg/m²). Patients had received a median of three prior therapies (range 1–4) which included alkylator therapy in all (five patients refractory) and fludarabine in four (all refractory). Therapy was tolerated well in all patients without decrement in cellular immune function or significant infectious morbidity. Partial responses were noted in three of these patients, including two with fludarabine-refractory disease. The median progression-free survival for these patients was 6.6 months (range 2.2–29+ months). These data suggest that rituximab has clinical activity in heavily pre-treated patients with Waldenstrom's macroglobulinemia. Based on these data, clinical studies of Rituximab in previously untreated and treated WM appear indicated.     

美罗华联合CHOP方案治疗B细胞性非霍奇金淋巴瘤效果观察

目的：探讨美罗华联合CHOP方案治疗B细胞性非霍奇金淋巴瘤的临床效果及不良反应。方法选择B细胞性非霍奇金淋巴瘤60例随机分成观察组和对照组各30例。观察组采用美罗华联合CHOP方案治疗,对照组仅采用CHOP方案治疗,比较两组临床疗效及不良反应情况。结果观察组患者临床疗效明显优于对照组（ P＜0.05）;不良反应除发热例数多于对照组外（ P＜0.05）,其余两组比较差异无统计学意义（P＞0.05）。结论对B细胞性非霍奇金淋巴瘤患者采用美罗华联合CHOP方案治疗,能够有效提高患者的临床疗效,值得临床推广。     

R+DA-EPOCH方案治疗弥漫大B细胞淋巴瘤的疗效

目的 探讨R+DA-EPOCH方案治疗弥漫大B细胞淋巴瘤（DLBCL）的临床疗效和安全性。方法 选择2015年5月至2018年1月中国科学技术大学附属第一医院西区（安徽省肿瘤医院）收治的30例初治DLBCL患者,采用R+DA-EPOCH方案治疗,评价临床疗效与安全性。结果 30例患者中,完全缓解（CR）14例（46.67%）,部分缓解（PR）7例（23.33%）。双重表达淋巴瘤患者治疗有效率为92.31%,非双重表达淋巴瘤患者治疗有效率为52.94%,差异具有统计学意义（P<0.05）。24个月的无进展生存期（PFS）率为86.54%,至随访终点的PFS率为78.67%。结论 R+DA-EPOCH方案对于DLBCL的有效率较高,尤其可克服双重表达对疾病预后的影响,不良反应可耐受,安全性高,值得临床推广应用。     

GemOx±R方案治疗复发或难治的侵袭性非霍奇金淋巴瘤

目的：观察GemOx±R方案治疗复发或难治的侵袭性非霍奇金淋巴瘤（NHL ）的近期疗效和不良反应。方法：经组织学证实的复发或难治的侵袭性29例NHL 患者给予GemOx±R方案：吉西他滨（gemcitabine ）1 000mg/m2,静脉注射,d1、d8;奥沙利铂（oxaliplatin）130mg/m2,静脉注射d1;加/不加利妥昔单抗（rituximab ）375mg/m2,静脉注射,d0。21~28d 为一个周期。每个患者均完成≥2 周期的化疗。结果：29例患者中,总有效率为65.5% ,11例完全缓解（CR）,8 例部分缓解（PR）;B 细胞和T 细胞淋巴瘤患者的有效率分别为68.4% 和60.0% ,差异无统计学意义（P>0.05）;但在B 细胞淋巴瘤中,加用美罗华与否的有效率分别为80.0% 和55.6% ,差异有统计学意义（P=0.043）。 不良反应主要表现为骨髓抑制和胃肠道反应,表现为粒细胞、血小板减少及恶心、呕吐等。结论：GemOx±R方案高效低毒,是针对复发或难治性的侵袭性非霍奇金淋巴瘤安全有效的解救方案。     

Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence

Autoimmune pancreatitis (AIP) is a type of immune-mediated pancreatitis subdivided into two subtypes, type 1 and type 2 AIP. Furthermore, type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4 (IgG4)-related disease. Nowadays, AIP is increasingly researched and recognized, although its diagnosis represents a challenge for several reasons: False positive ultrasound-guided cytological samples for a neoplastic process, difficult to interpret levels of IgG4, the absence of biological markers to diagnose type 2 AIP, and the challenging clinical identification of atypical forms. Furthermore, 60% and 78% of type 1 and type 2 AIP, respectively, are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer. As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging, obtaining a definitive diagnosis can therefore prove difficult, since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal. This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence, new serum markers, and new therapeutic approaches, while it also outlines the current management recommendations. A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse, although such an approach requires close collaboration between gastroenterologists, surgeons and radiologists. Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.