R-GemOx与RICE方案二线治疗复发或难治性弥漫大B细胞淋巴瘤的临床对比研究

对比美罗华联合奥沙利铂和吉西他滨（R-GemOx）与RICE方案二线治疗复发或难治性的弥漫大B细胞淋巴瘤（DLBCL）的疗效及毒副作用。方法：选取复发或难治性弥漫大B细胞淋巴瘤患者65例,随机分为两组,分别接受R-GemOx方案和RICE方案化疗。R-GemOx组方案为：美罗华,375 mg/m2静脉滴注,d0,吉西他滨（GEM）1 000 mg/m2,静脉滴注,d1、8;奥沙利铂（L-OHP）130 mg/m2,静脉滴注,d1;21天为1周期。RICE组方案为：美罗华,375 mg/m2,静脉滴注,d0;异环磷酰胺（IFO ）1 g/m2,静脉滴注,d1～d3;Mesna解救400mg,静脉滴注q8h,d1～d3;卡铂（CBP）,AUC=5,静脉滴注,d2;依托泊苷（VP-16 ）100mg/m2,静脉滴注,d1～d3。21天为1个周期。每2周期进行疗效及毒性评价。结果：65例患者中,R-GemOx方案组,完全缓解（CR）4例（12.5%）,部分缓解（PR）17例（53.1%）,稳定（SD）6例,进展（PD）5例,总有效率（CR+PR）为65.6%,临床获益率（CR+PR+SD）达到84.4%。RICE组CR 4例（12.1%）,PR 16例（48.5%）,SD 7例,PD 6例,总有效率60.6%,临床获益率81.8%。两组的不良反应主要为骨髓抑制,其中R-GemOx组白细胞下降Ⅲ度5例,Ⅳ度2例;贫血Ⅲ度2例;血小板下降Ⅲ度4例,Ⅳ度2例。RICE组白细胞下降Ⅲ度16例,Ⅳ度5例;贫血Ⅲ度2例;血小板下降Ⅲ度5例,Ⅳ度3例。胃肠道反应RICE组较R-GemOx组为重,其中Ⅲ度2例,Ⅳ度1例。比较两组毒副反应,R-GemOx组在中性粒细胞减少,消化道反应方面明显好于RICE组（P<0.05）。而RICE组未出现一例末梢神经毒性。结论：R-GemOx方案是二线治疗复发或难治性弥漫大B细胞淋巴瘤较为安全且有效的化疗方案,其远期疗效尚需进一步观察。     

The role of complement in the mechanism of action of rituximab for B-cell lymphoma: implications for therapy

Rituximab, a genetically engineered chimeric monoclonal antibody specifically binding to CD20, was the first antibody approved by the U.S. Food and Drug Administration for the treatment of cancer. Rituximab significantly improves treatment outcome in relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). However, there are also some challenges for us to overcome: why approximately 50% of patients are unresponsive to rituximab in spite of the expression of CD20, and why some responsive patients develop resistance to further treatment. Although the antitumor mechanisms of rituximab are not completely understood, several distinct antitumor activities of rituximab have been suspected, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), apoptosis, and direct growth arrest. To counteract resistance to rituximab therapy, several strategies have been developed to: (a) augment the CDC effect by increasing CD20 expression, heteroconjugating rituximab to cobra venom factor and C3b, and inhibiting membrane complement regulatory protein, especially CD59, function; (b) enhance the ADCC effect through some immunomodulatory cytokines and CR3-binding beta-glucan; and (c) reduce the apoptotic threshold or induce apoptotic signaling on the tumor. Extensive studies indicate that rituximab combined with these approaches is more effective than a single rituximab approach. Herein, the mechanism of action of and resistance to rituximab therapy in B-cell NHL, in particular, the involvement of the complement system, are extensively reviewed.     

Myelopathy from Waldenström's macroglobulinemia: improvement after Rituximab therapy

Approximately 20% of patients with Waldenström's macroglobulinemia (WM) have neurological complications; primarily peripheral neuropathies and symptoms related to a hyperviscosity syndrome. We report a rare case of a patient presenting with a slowly progressive myelopathy due to WM who had a marked response to Rituximab therapy.     

Anti-CD20 Monoclonal Antibody (Rituximab) for Therapy of Mediastinal CD20-Positive Large B-Cell Non-Hodgkin Lymphoma with a Local Tumor Extension into the Lung of a 10-Year-Old Girl

Intravenous therapy with the anti-CD20 antibody Rituximab has been recently approved for the treatment of CD20 positive non-Hodgkin's lymphoma (NHL) in adults but not in children. The authors present the benefits of its application for mediastinal NHL CD 20+ with a local extension into the lung of a 10-year-old-girl. Receiving the chemotherapy according to study NHL-BFM-95 for high-risk lymphoma the girl did not reach complete remission. Before the last chemotherapy block was started, a computed tomography scan of the thorax showed residue in the right lung. Twenty-five days after the last chemotherapy she received Rituximab at a dose of 375 mg/m 2 by intravenous infusion once a week for a total of four doses without the adverse reactions. Complete remission was achieved. The patient was high risk with lung involvement of lymphoma suggesting a pure prognosis. The results suggest that Rituximab may improve the outcome in high-risk patients and appeared to be safe and effective in children also.     

新型前哨淋巴结示踪剂的制备及动物实验研究

背景与目的：前哨淋巴结活检是临床腋窝淋巴结阴性早期乳腺癌患者治疗的标准。准确定位前哨淋巴结对分期、预后及治疗至关重要。该研究将利妥昔单抗与荧光示踪剂吲哚菁绿偶联,制备新型前哨淋巴结示踪剂,确定最佳偶联比例,并对其生物学特性、安全限度及定位性能进行研究。方法：直接偶联法制备新型前哨淋巴结吲哚菁绿-利妥昔单抗,双层析快速薄层层析-硅胶层析纸法测定标记率,非还原型SDS聚丙烯酰胺凝胶电泳法和双抗体夹心间接酶联免疫测定法检测新型示踪剂中单抗分子完整性和免疫活性,按中华药典要求检测新型示踪剂的安全限度及在小鼠体内前哨淋巴结的定位性能。结果：新型示踪剂中利妥昔单抗分子完整且保持了单抗的免疫活性,利妥昔单抗大分子上吲哚菁绿的标记率为100%,新型示踪剂为无菌、无致热原的溶液且局部注射不会产生危害。利妥昔单抗与吲哚菁绿质量比例为4∶1、6∶1偶联形成的新型示踪剂,前哨淋巴结显像效果最佳。前哨淋巴结定位与核素法一致。结论：吲哚菁绿-利妥昔单抗偶联的新型前哨淋巴结示踪剂的制备工艺简单且无放射性危害,其中单抗的分子完整性和免疫活性无破坏,为无菌、无致热原、无急性毒性的示踪剂,能够用于前哨淋巴结显像。     

Spontaneous bacterial peritonitis from Salmonella: an unusual bacterium with unusual presentation

Spontaneous bacterial peritonitis (SBP) is a common cause of morbidity and mortality in patients with advanced cirrhosis and portal hypertension. While gram-negative rods and Enterococcus species are the common offending organisms, Salmonella has also been recognized as a rare and atypical offending organism. Atypical features of Salmonella SBP include both its occurrence in cirrhotic patients with immunosuppressive state and its lack of typical neutroascitic response. Diagnosis is often delayed as it requires confirmation from ascitic fluid culture. We report a case of Salmonella SBP occurring in a patient with decompensated cryptogenic cirrhosis with concurrent low-grade non-Hodgkin lymphoma and prior treatment with rituximab. Physicians should be aware of the atypical presentation, especially in cirrhotic patients who are immunosuppressed.     

去B细胞治疗在系统性红斑狼疮治疗中的研究进展

B细胞在系统性红斑狼疮(SLE)的发病过程中具有重要作用。目前临床应用的主要的去B细胞生物治疗包括抗CD20单抗、抗CD22单抗、抗B细胞活化因子单抗。多数研究显示去B细胞治疗可以改善常规治疗无效的SLE患者的病情,对狼疮肾损害及中枢神经系统损害有治疗作用,多数患者耐受性较好,治疗失败的原因与实验设计、抗体产生等有关。     

中期PET/CT检查在以R-CHOP为一线治疗弥漫大B细胞淋巴瘤患者预后评估中的作用

以临床特征为基础的国际预后指数（internationalprognosticindex,IPI）用于弥漫大B细胞淋巴瘤（diffusedlargeB．celllymphoma,DLBCL）患者预后的评价,但相同IPI积分患者的预后存在着差别。