Rituximab, a chimeric mouse-human anti-CD20 monoclonal antibody

CD20 antigen is expressed on nearly all human B-cells and B-lymphoma cells. Rituximab is a chimeric anti-CD20 monoclonal antibody with mouse variable and human constant regions. The toxicities of rituximab are mainly infusion-related, non-hematological grade 1 or 2 episodes. Of the 11 eligible patients enrolled in the phase I study in Japan, 2 showed CR and 5 showed PR. 90 relapsed pts were enrolled in the subsequent phase II study and treated with rituximab at 375 mg/m2 x 4 weekly infusions. The overall response rates in relapsed indolent B-cell lymphoma and mantle cell lymphoma were 61%(37/61) and 46%(6/13), respectively. Rituximab is a novel, effective anti-lymphoma agent with acceptable toxicities.     

嵌合型抗-CD20单抗联合化疗治疗5例难治性淋巴瘤

目的：观察嵌合型抗－CD20单抗（Rituximab,IDEC-C2B8,美罗华）联合以CHOP为主的化疗方案或联合自体外周血干细胞移植（APBSCT）治疗难治性弥漫性大B细胞淋巴瘤（DLBCL）的临床疗效和毒副作用。方法：选择5例难治性DLB－CL，第1天予美罗华375mg/m^2，第3天起给CHOP方案或ICEP方案化疗，间歇3周重复用药，共4－6个疗程。结果：完全反应率100％，2例CR，3例PR。仅1例发生持续中性粒细胞减少。结论：美罗华联合化疗治疗难治性DLBCL具有显著疗效，而且没有增加化疗的毒副作用。     

R-CHOP方案与CHOP方案治疗初治弥漫性大B细胞淋巴瘤的临床研究

为比较利妥昔单克隆抗体联合标准CHOP方案与标准CHOP方案治疗初治CD20阳性的弥漫慢大B细胞淋巴瘤（DLBCL）患者的疗效和安全性，采用同期（2003年7月至2006年12月）非随机对照的前瞻性研究方法，将69例在我院住院的初治DLBCL患者分为R—CHOP组和CHOP组，其中CHOP组36例，R—CHOP组33例，比较两组的完全缓解率、生存期及不良反应情况。结果显示：R—CHOP组23例（69．7％）获完全缓解（CR），部分缓解（PR）6例（18.2％），总有效率为88．5％，高于CHOP组；CHOP组17例（47．2％）获CR，11例（30．6％）获PR，总有效率77．8％（P=0.049）。尤其在男性、AnnArbor Ⅲ—Ⅳ和IPI3—5分的患者中，R—CHOP方案的CR率明显高于CHOP方案，且差异具有统计学意义（P=0．017、P=0．005和P=0．000）。R—CHOP组预计的平均生存时间（OS）为45．7个月，长于CHOP组的35．2个月，但经Log—Rank检验，差异无统计学意义（P=0．145）；R—CHOP组预计的平均无疾病进展生存时间（PFS）为38．5个月，长于CHOP组的24．6个月，经Log—Rank检验，差异有统计学意义（P=0.017）。R—CHOP组的不良反应主要为发热等输注相关的不良反应，而骨髓抑制情况与CHOP组类似：结论：利妥昔单克隆抗体联合CHOP方案治疗CD20阳性的DLBCL与单纯CHOP方案相比，能显著提高疗效，同时并不增加化疗的毒副反应。     

美罗华联合ICE方案治疗复发非霍奇金淋巴瘤疗效观察

目的观察和评价美罗华联合ICE方案治疗复发非霍奇金淋巴瘤(NHL)疗效及不良反应。方法 20例复发性NHL患者采用美罗华联合ICE方案化疗。美罗华375 mg/m2,静脉滴注,第1天;异环磷酰胺1.5 g/m2,静脉滴注,第2~4天;卡铂200 mg/m2,避光静脉滴注,第2~4天;依托泊苷,100 mg/m2,静脉滴注,第2~4天。21~28 d为1个周期,每例患者至少完成2个周期以上治疗后评价临床疗效及不良反应发生情况。结果 20例患者中,完全缓解6例,部分缓解7例,无变化3例,进展4例,临床总有效率为65.0%。主要不良反应为骨髓抑制,主要表现为白细胞减少和血小板减少,其次为恶心呕吐,心脏、肝脏、肾脏、神经毒性和皮肤黏膜炎较少见。随访至2012年8月,中位生存期14个月。结论美罗华联合ICE方案可作为复发性中高度恶性NHL的治疗方案。     

A prospective clinical trial evaluating the safety and efficacy of the combination of rituximab and plerixafor as a mobilization regimen for patients with lymphoma

BACKGROUND: Previous reports suggested that rituximab may impair stem cell collection and posttransplant engraftment in lymphoma patients undergoing autologous hematopoietic progenitor cell transplantation. STUDY DESIGN AND METHODS: A prospective biologic allocation study examined the effect of adding rituximab to a mobilization regimen of plerixafor and granulocyte–colony‐stimulating factor (G‐CSF) for patients with CD20+ lymphoma compared with CD20? lymphoma patients mobilized without rituximab. The primary endpoint was safety of the rituximab‐containing regimen; secondary endpoints compared the efficiency of stem cell collection, posttransplant engraftment, graft characteristics, mobilization kinetics, immune reconstitution, and engraftment durability between the cohorts of patients with CD20+ and CD20? lymphoma. RESULTS: Fifteen subjects assigned to each treatment arm were accrued. Both mobilization regimens had similar toxicities. The median number of CD34+ cells collected (7.4 × 10⁶/kg vs. 6.4 × 10⁶/kg) and the median numbers of days of apheresis needed to collect stem cells were not different between the CD20+ and CD20? cohorts. No significant differences in neutrophil engraftment (median, 13.5 days vs. 13 days) or platelet engraftment (22 vs. 21 days) or in graft durability were seen comparing patients with CD20+ versus CD20? lymphoma. There were no significant differences in the kinetics of blood T‐cell or natural killer–cell reconstitution comparing the two groups. B‐cell reconstitution was delayed in the CD20+ lymphoma group, but this did not translate into a significant increase in infectious complications. CONCLUSION: Rituximab can be safely added to the combination of plerixafor and G‐CSF as a mobilization strategy without excess toxicity or posttransplant engraftment delays for patients with chemosensitive lymphoma undergoing autologous hematopoietic progenitor cell transplantation.     

利妥昔单克隆抗体治疗难治复发性特发性血小板减少性紫癜临床疗效初步评估

本研究评价利妥昔单克隆抗体治疗难治复发性特发性血小板减少性紫癜(ITP)的临床疗效。选择我院2007年1月-2010年12月期间确诊为难治、复发性ITP患者18例,给予利妥昔单克隆抗体375 mg/m2静脉滴注,每周1次,连用4周为1个疗程。结果表明,18例患者接受22个疗程的利妥昔单克隆抗体治疗,治疗有效率为68%,完全反应率为45%,部分反应和微小反应率为23%,无效率为32%。自利妥昔单克隆抗体治疗开始中位治疗反应时间为3周(1-17周),中位疗效持续时间13周(1周-42个月)。大多数反应持续时间短,随访中位时间20个月(1-52个月),36%患者的治疗反应维持时间超过6个月,27%患者的治疗反应维持时间超过1年,随访结束,4例患者存在持续疗效。未行脾切除患者对利妥昔单克隆抗体治疗反应较脾切除患者好(P=0.037)。应用利妥昔单克隆抗体治疗失败及应用多种治疗手段包括脾切除的ITP患者后续治疗效果差。结论:利妥昔单克隆抗体治疗难治性、复发性ITP,疗效较好,患者容易耐受,20%左右患者有远期疗效。利妥昔单克隆抗体治疗失败ITP患者的后续治疗效果差。     

The therapeutic use of rituximab in non-Hodgkin's lymphoma

The non-Hodgkin's lymphomas (NHLs) comprise a heterogeneous collection of lymphoproliferative malignancies, which are most common in people aged over 55 years. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL, accounting for approximately 30% of all new patients. Follicular lymphoma (FL) is the second most common NHL sub-type, and accounts for a further 22% of cases. While the incidence of most other cancers is decreasing, that of NHL is increasing steadily. During the 1970's and 1980's, worldwide NHL incidence rose by 3-4% per year. This rise has slowed in the 1990's, but an annual increase of 1-2% is still being recorded. Over the last five years, the introduction of monoclonal antibodies, and specifically the anti-CD20 monoclonal antibody, rituximab, has radically changed treatment of B-cell NHL. Rituximab is a genetically engineered chimeric mouse/human monoclonal antibody which binds to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes. This antigen is expressed on over 95% of all B cell NHLs, and on normal B cells, but not on haematopoietic stem cells, normal or malignant plasma cells. The Fc domain of rituximab recruits immune effector functions to mediate B cell lysis. Possible mechanisms of cytotoxicity include complement-dependent cytotoxicity (CDC) resulting from C1q binding, and antibody-dependent cellular cytotoxicity (ADCC) mediated by one or more of the Fcgamma receptors on the surface of granulocytes, macrophages and NK cells. It is also possible that the binding of rituximab to the CD20 antigen on the cell surface may directly induce apoptosis. For patients with both follicular and diffuse large B-cell NHL, several large scale prospective randomised trials have demonstrated prolongation of remission when rituximab is incorporated into first line treatment, and, in follicular lymphoma, as a component of salvage therapy. As a result of these studies, current European indications for rituximab include: the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with cyclophosphamide, vincristine and prednisone (CVP) chemotherapy; as maintenance therapy in patients with relapsed follicular lymphoma responding to induction therapy with chemotherapy or immuno-chemotherapy; the treatment of patients with diffuse large B cell NHL in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This paper examines the evidence supporting the use of rituximab in these settings, and places its use into the context of standard clinical practice.     

利妥昔单抗联合自体外周血造血干细胞移植治疗高危侵袭及难治复发性B-NHL的疗效分析

目的:探讨利妥昔单抗(R)联合自体外周血造血干细胞移植(auto-HSCT)治疗高危侵袭性及难治复发CD20+B细胞非霍奇金淋巴瘤(B-NHL)的疗效.方法:选取本中心2005年1月-2013年12月确诊为高危侵袭性及难治复发CD20+B-NHL、并行auto-HSCT治疗的患者资料83例.联合R治疗的患者为观察组,共...     

Use of Mabtera (rituximab) in treating patients with refractory courses of B-cell lymphoma,along with high-dose chemotherapy and autologous transplantation of hematopoietic stem cells

AIM: To study efficacy of rituximab in patients with resistant B-cell lymphoma on high-dose chemotherapy. MATERIAL AND METHODS: From September 2000 to April 2002 we studied efficacy and tolerance of rituximab at different stages of high-dose chemotherapy. The treatment was given to 10 patients with histologically verified CD20+ non-Hodgkin's lymphoma: diffuse large-cell (n = 4), Berkitt's (n = 2), follicular (n = 3), mantle-cell (n = 1). Five patients with diffuse large-cell lymphoma and Berkitt's lymphoma had a primary resistant course of the disease, one patient with diffuse large-cell lymphoma had a refractory recurrence. Follicular and mantle-cell lymphomas were characterized by a resistant course and large tumor masses. The patients received 1-2 courses of induction chemotherapy with dexa-BEAM with collection of peripheral stem cells followed by high-dose chemotherapy (BEAM-9, CBV + mitoxantron-1) with transplantation of autologous stem blood cells. Rituximab infusion (375 mg/m2) was conducted before the collection of the stem cells, prior to high-dose chemotherapy and in posttransplantation period after recovery of hemopoiesis. RESULTS: 4 patients achieved complete remission, 3-partial remission, 2 had progression and 1-stabilization. In mean follow-up 11 (2-20) months 7 of 10 patients were alive, overall survival being 15 +/- 2.4 months (95% confidence interval 10-19.7), median was not reached. 5 patients are in complete remission: 2 of them without further treatment, 3-after progression and repeat therapy including rituximab and interferon-alpha or rotuximab and CHOP chemotherapy. CONCLUSION: The addition of rituximab can improve the results of high-dose chemotherapy of patients with non-Hodgkin's lymphoma resistant to standard doses of cytostatics. Repeat use of this drug can be effective in some patients with progression after high-dose chemotherapy with rituximab.     

Development of monoclonal antibody therapy for malignant lymphoma

Lymphomas are among the tumors most responsive to chemotherapeutic agents and radiation therapy. Despite chemotherapeutic and radiological advances, tumor cell resistance still remains a problem, and the toxicity of chemotherapy and radiation therapy limits their potential. Less toxic therapies for lymphoma have been continued to search for effectiveness. Since the discovery of the hybridoma technology by Kohler and Milstein in 1975, utilizing antibodies as targeted therapy for lymphoma has been investigated for many years. After 20 years of clinical trials, monoclonal antibody therapy of lymphoma enters the new millennium ready for 'prime time'. Investigators' early enthusiasm was dampened by problems with tumor targeting, HAMA, and allergic reactions, but important advances in molecular biology and chelation chemistry have led to new and improved reagents. Rituximab(IDEC-C2B8) has already been approved by the FDA in USA and the Ministry of Welfare and Labour in Japan for relapsed CD20-positive lymphomas and indolent B-cell lymphoma including mantle cell lymphoma, respectively. Ibritumomab tiuxetan and iodine-131 anti-B1 antibody have an excellent anti-lymphoma profile, and both appear to have higher response rates than rituximab. Results from the rituximab vs. ibritumomab tiuxetan phase III trial clearly favor the latter especially in %CR. Radiolabeled Lym-1, T101, LL2, and anti-Tac data will be forthcoming. Continued refinements of immunotoxins will establish their possible therapeutic role, and a variety of antibody conjugates including drugs, prodrugs, nonprotein toxins, and other agents, will continue to be studied in the clinic. Bispecific antibodies for lymphoma are also in early clinical testing. Over the next 10 years, many of the major advances in lymphoma therapy will be antibody-based.     

Obinutuzumab for the treatment of lymphoproliferative disorders

INTRODUCTION: Targeted therapy against CD20 with the mAb rituximab has led to significant improvements in survival for patients with B-cell non-Hodgkin's lymphoma (NHL). Despite these improvements, many patients relapse and/or become refractory after rituximab-containing therapies and thus better therapies are required for NHL. AREAS COVERED: Obinutuzumab is a novel, humanized, anti-CD20 mAb currently being investigated in Phase III studies in comparison to rituximab. An overview of obinutuzumab, its mechanisms of action and the results of pre-clinical and Phase I/II studies are presented. EXPERT OPINION: Pre-clinical studies suggest that obinutuzumab is a more potent anti-CD20 mAb than Rituximab at inducing antibody-dependent cellular cytotoxicity (ADCC) and direct cell death (DCD). Obinutuzumab is safe and effective in CD20 + NHL and further study is warranted. Results of ongoing Phase III clinical trials comparing Obinutuzumab to Rituximab in different disease settings and with different chemotherapy regimens are eagerly awaited.     

急性毒性反应在利妥昔单抗联合化疗治疗恶性淋巴瘤中的护理

目的观察恶性淋巴瘤患者应用利妥昔单抗联合化疗治疗出现的急性毒性反应并探讨相关护理措施。方法回顾性分析20例应用利妥昔单抗联合化疗的恶性淋巴瘤患者的临床资料,观察治疗期间出现的急性毒性反应。结果本组20例患者治疗期间主要毒性反应为变态反应35%、胃肠道反应65%、骨髓抑制80%,心血管反应15%,所有患者均顺利完成靶向药物及化疗治疗。结论利妥昔单抗联合化疗的急性毒性反应发生率较高,护士的密切观察、严格的用药管理、及时有效的护理措施是保证治疗安全的重要基础。     

CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications

Clonotypic B cells circulating in patients with multiple myeloma (MM) express CD20, and it has been suggested that these cells may be clonogenic. Furthermore, 20% of patients with MM express CD20 on their bone marrow plasma cells (BMPCs). Therefore, the authors began a phase II clinical study to determine the activity of the anti-CD20 monoclonal antibody rituximab in MM patients. Nineteen previously treated MM patients received 375 mg/m2 rituximab per week for 4 weeks. Three months after initiation of treatment, patients were assessed for response and received a second course of therapy if their disease was stable (SD) or they achieved a partial response (PR). Six of 19 (32%) patients had either a PR (n = 1) or SD (n = 5), with a median time to treatment failure of 5.5 months (mean, 10.3 months; range, 3-27+ months). All six patients who had a PR or SD had CD20+ BMPC. Overall, rituximab therapy was well tolerated. Because most patients with MM poorly express CD20 on their BMPCs, the authors evaluated agents for their ability to induce CD20 expression and thereby facilitate rituximab binding on MM cells. These studies show that interferon-gamma (IFN-y) induced CD20 expression on MM BMPCs, MM B cells, and healthy donor BMPCs. In contrast, CD20 expression on chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma, healthy donor B cells, and progenitor cells was unaffected by IFN-y. Rituximab binding to the BMPCs of MM patients was also increased after culture with pharmacologically attainable levels of IFN-gamma (1-100 U/mL). In conclusion, these studies suggest that MM patients with CD20+ BMPCs may benefit from rituximab therapy. Furthermore, IFN-gamma induces CD20 expression on MM BMPCs and B cells and facilitates rituximab binding to MM BMPCs, providing the rationale for clinical trials to examine its use with CD20-directed serotherapies in MM.     

慢性B细胞淋巴增殖性疾病合并自身免疫性溶血性贫血

本研究探讨慢性B细胞淋巴增殖性疾病（B-CLPD）并发自身免疫溶血性贫血（AIHA）的临床特征,提高对该疾病的认识。回顾性分析2000年至2012年治疗的B-CLPD合并AIHA患者14例,分析其临床特征、实验室检查结果、治疗及转归。结果表明,14例AIHA患者中慢性淋巴细胞白血病（CLL）9例、淋巴瘤5例;溶血发作时血红蛋白中位数61（33-84）g/L,网织红计数比例中位数12.0（3.1-35.0）%,Coombs试验阳性率100%;1例患者单用糖皮质激素治疗,5例采用化疗联合糖皮质激素治疗,8例采用利妥昔单抗免疫化疗联合糖皮质激素治疗,有效率达100%,其中完全缓解率78.6%（11/14）,部分缓解率21.4%（3/14）;随访至今,35.7%（5/14）出现溶血再发,经用既往治疗方案仍有效,应用过利妥昔单抗治疗的病例仅1例复发;14例中已有6例死亡,1例失访,其余7例存活。结论：AIHA是B-CLPD的常见并发症,可在疾病不同阶段出现。糖皮质激素免疫抑制剂疗效较好,但长期缓解率低,停药或减量后易复发,单克隆抗体具有较好的应用前景。     

Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.     

R-CHOP方案治疗17例弥漫大B细胞型淋巴瘤临床观察

目的研究利妥昔单抗联合CHOP方案治疗弥漫大B细胞型淋巴瘤的疗效和不良反应。方法17例弥漫大B细胞型淋巴瘤(DLBCL)共接受6个周期R-CHOP方案的治疗:利妥昔单抗375mg/m2第1天,环磷酰胺750mg/m2第2天,阿霉素50mg/m2第2天,长春新碱1.4mg/m2第2天,泼尼松100mg/d第2～6天。结果总缓解率为82.4%,其中完全缓解9例,完全缓解率为52.9%,5例达到部分缓解,部分缓解率29.4%。17例患者1年和2年无进展生存率分别为82.4%(14/17)和58.8%(10/17),1年和2年的总生存率分别为94.1%(16/17)和76.5%(13/17)。其不良反应主要为骨髓抑制,仅1例出现利妥昔单抗输注相关反应。结论R-CHOP方案治疗弥漫大B细胞型淋巴瘤疗效高而不良反应轻,可作为治疗该病的一线方案。     

自体造血干细胞移植联合利妥昔单抗治疗非霍奇金淋巴瘤6例(英文)

背景:利妥昔单抗单用或联合CHOP方案化疗治疗CD20阳性非霍奇金淋巴瘤已取得较好疗效,非霍奇金淋巴瘤经自体造血干细胞移植治疗同样可以提高患者的疗效和生存率,而将两种方法联合的效果尚存在争论.目的:探讨自体造血干细胞移植联合利妥昔单抗对CD20阳性非霍奇金淋巴瘤的有效性.方法:对6例CD20阳性非霍奇金淋巴瘤Ⅳ期患者进行自体造血干细胞移植的同时,联合使用利妥昔单抗,分别于移植前给予2～4次,动员和预处理前后各2次,移植后每3个月维持治疗1次,利妥昔单抗用量为 375 mg/m~2静滴.结果与结论:平均采集单个核细胞数为5.13×10~(-8)/kg,CD34~+细胞数为4.75×10~(-6)/kg.6例患者自体造血干细胞移植后,造血功能均恢复顺利,中性粒细胞计数大于0.5×10~(-9)L~(-1)为移植后9～15 d,血小板计数大于20×10~(-9)L~(-1)为移植后12～19 d.6例患者在移植过程中均未发生出血性膀胱炎、间质性肺炎、巨细胞病毒感染和肝静脉阻塞等并发症.利妥昔单抗使用过程中,无发热、寒战、皮疹等不良反应发生.移植后6～32个月,患者均处于完全缓解状态.提示自体造血干细胞移植并利妥昔单抗治疗CD20阳性非霍奇金淋巴瘤是一种较好的方法,可维持治疗效果,有利于防止复发.     

Rituximab for chronic lymphocytic leukemia

INTRODUCTION: Rituximab is a high-affinity chimeric mouse anti-CD20 monoclonal antibody, currently used for the treatment of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and autoimmune disorders. AREAS COVERED: This article summarizes recent achievements in the clinical activity and toxicity of rituximab in the treatment of patients with CLL. A literature search was conducted of the PubMed MEDLINE database for articles in English. Publications from 2000 through January 2012 were scrutinized. The search terms used were rituximab in conjunction with chronic lymphocytic leukemia or CLL. Conference proceedings from the previous 5 years of The American Society of Hematology, The European Hematology Association, and American Society of Clinical Oncology were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. EXPERT OPINION: Rituximab is an active drug in CLL when used as a single agent and in combination with chemotherapy, particulary with fludarabine or fludarabine and cyclophosphamide (R-FC regimen). In addition, rituximab may be an optimal therapeutic choice of treatment for CLL-associated autoimmune cytopenias.     

抗CD20单克隆抗体提高淋巴瘤细胞对X射线的敏感性

本研究观察抗CD20单克隆抗体制剂利妥昔（RTX）对X射线所致的人淋巴瘤细胞损伤的影响。用SRB法检测细胞存活,FITC-Annexin—V／PI试剂盒测定细胞凋亡,透射电子显微镜观察细胞形态,激光共聚焦显微镜检测胞质内钙离子浓度。结果显示,RTX可明显增强X射线时的肿瘤细胞生长抑制作用（P〈0．05）;与单照射组比较,RTX可增加辐射诱导的细胞凋亡;透射电子显微镜下可见多种凋亡表现;细胞内[Ca^2＋]离子明显升高。结论：RTX可提高淋巴瘤细胞对X射线的辐射敏感性,诱导较多细胞的凋亡,并且与细胞内钙离子的变化有关。     

标准剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床研究

目的 探讨标准剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症(ITP)的疗效、安全性及治疗前后B细胞、血小板膜糖蛋白特异性自身抗体的变化.方法 利妥昔单抗每周375 mg/m2,静脉滴注,连用4周,治疗31例复发难治性ITP患者,不伴随使用免疫抑制剂、化疗药、抗凝药及激素冲击疗法.监测治疗前后的血常规,血清免疫球蛋白(IgG、IgM、IgA),血小板GPⅡb/Ⅲa和(或)GP Ⅰb/Ⅸ特异性自身抗体及CD3+、CD4+、CD8+、CD19+、CD20+细胞数.结果 12例完全有效,7例有效,12例无效.中位疗效持续时间6(2～48)个月,有效患者4例复发,其余疗效均维持较好.有效患者治疗后血小板自身抗体均转阴.治疗前后外周血血红蛋白、白细胞计数无明显变化,血清IgG、IgM、IgA无明显变化,CD3+、CD4+、CD8+细胞数无明显变化.治疗后CD19+/CD20+细胞明显下降.多数患者耐受好.结论 利妥昔单抗治疗复发难治性ITP疗效肯定,不良反应可以耐受.

Abstract：

Objective To evaluate the efficacy and safety of rituximab on B-lymphocytes and antiplatelet glycoprotein-specific antibodies in patients with refractory primary immune thrombocytopenic (ITP).Methods Thirty-one ITP patients with a median age of 36 years (range 16 -56 years) received solely intravenous rituximab at the dose of 375 mg/m2 once weekly for consecutive 4 weeks. Lab studies included complete blood count, serum concentrations of IgG, IgM and IgA. CD3+ , CD4 + , CD8 + , CD19 + and CD20 +cell numbers were assayed by flow cytometry and anti-platelet glycoprotein-specific antibodies ( GP Ⅱ b/Ⅲ a,GP Ⅰ b/Ⅸ ) were assayed by monoclonal antibody-specific immobilisation of platelet antigens (MAIPA) prior to and following rituximab therapy. The response was evaluated according to the response criteria of international working group of ITP. Results Complete responses were achieved in 12 cases, response in 7 cases,and no response in 12 cases. Responses were sustained 2 to 28 months ( median 6 months) with 4 cases relapsed. After 4 weeks of rituximab therapy, GP Ⅱ b/Ⅲ a and GP Ⅰ b/Ⅸ disappeared in responded patients, and CD 19 +/CD20+ cells were almost depleted in all patients. As expected, the serum concentrations of IgG, IgM2 IgA, and the T cell counts were not changed after therapy. Four patients developed infusion-related reaction, 1 impaired renal function, and 3 secondary infections. Conclusion Rituximab is effective and safe, and the adverse reaction is tolerable.