美罗华联合化疗方案治疗B型非霍奇金淋巴瘤急性不良反应的观察与护理

非霍奇金淋巴瘤(NHL)是临床常见的恶性肿瘤之一。NHL的来源包括B淋巴细胞型和T淋巴细胞型,其中B淋巴细胞型占80%[1]。95%以上的B淋巴细胞型NHL表达CD20抗原[2]。美罗华是一种嵌合型鼠/人单克隆抗体,它能特异性地与B淋巴细胞表面CD20抗原结合,并通过人体的免疫细胞和免疫因子清除肿瘤细胞。因此,美罗华成为过去20年治疗B淋巴细胞NHL的重要药物[3]。即使使用美罗华前后采取一系列措施,其急性不良反应仍时有发生,而且美罗华药价昂贵。如何在保证安全的前提下给予适当的干预,最大可能的使发生急性反应的患者继续完成治疗,从而     

利妥昔单抗与心血管事件

<正>利妥昔单抗(商品名:美罗华)是特异性作用于CD20抗原的单克隆抗体。CD20抗原是表达于人正常B细胞表面的一种跨膜蛋白,在B淋巴细胞的增殖、活化、分化及信号传递中起重要作用,是B细胞的特异性标志。CD20在90%以上的NHL的肿瘤性B细胞表面存在过表达,因此是利妥昔单抗治疗的理想的靶标,为B细胞NHL开创了免疫化疗的治疗新途径。随后进行的多项临床研究[1-3]也得到了令人鼓舞的结     

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。     

美罗华治疗非霍奇金淋巴瘤发生过敏反应1例护理

美罗华又名利妥昔单抗注射液,是一种人鼠嵌合性单克隆抗体,能特异性地与跨膜抗原CD20结合,启动介导B细胞溶解的免疫反应,适用于治疗复发或化疗耐药的B细胞非霍奇金淋巴瘤(NHL)[1]。NHL是一组起源于淋巴结和(或)结外淋巴组织的恶性肿瘤,其中绝大多数来源于B淋巴细胞[2],90%以上的患者表达     

利妥昔单抗在皮肤病中的治疗应用

利妥昔单抗是针对正常和恶性B淋巴细胞表面CD20抗原的鼠/人嵌合型单克隆抗体(mAb).它适用于治疗复发性或难治性、低度恶性或滤泡性、CD20阳性B细胞非霍奇金淋巴瘤,还常用于治疗慢性淋巴细胞白血病、原发性巨球蛋白血症和免疫性或特发性血小板减少性紫癜(ITP).利妥昔单抗能有效治疗原发性皮肤B细胞淋巴瘤和其他皮肤淋巴瘤以及混合型冷球蛋白血症,还可望用于治疗系统性红斑狼疮、皮肌炎、天疱疮、脉管炎和多种血液病.通常引起轻微皮肤不良反应,偶可引起副瘤天疱疮、Stevens-Johnson综合征、苔藓样皮炎、大疱性皮炎和中毒性表皮坏死松解症.     

利妥昔单抗治疗恶性淋巴瘤的进展

利妥昔单抗（人源化CD20单克隆抗体，商品名美罗华）是首个批准用于治疗表达CD20恶性淋巴省的单克隆抗体，广泛应用于低度恶性非雷奇金琳巴瘤（NHL）、侵袭性NHL，亦试用于霍奇金淋巴瘤（HL）及其他B细胞性恶性肿瘤。刊蚤昔单抗联合细胞毒性药物的疗效已在B细胞NHL的有关临床试验中得到证实。目前该药已被批准用于侵袭性淋巴瘤和惰性淋巴瘤的一线治疗，其维持治疗滤泡性淋巴瘤亦得出鼓舞人心的结果．利妥昔单抗已成为治疗B细胞性恶性淋巴瘤的重要手段之一。     

MabThera申请用于CLL

Roche公司在欧盟申请MabThera（rituximab）（I）作为一线治疗用于慢性淋巴细胞白血病（CLL）。（I）是一种单克隆抗体，与正常和恶性B细胞表面的CD20抗原结合，并募集人体的天然免疫防御将它们破坏。它目前仅用于治疗非何杰金淋巴瘤（NHL）。     

抗CD20单克隆抗体联合化疗及自体造血干细胞移植治疗恶性淋巴瘤

非霍奇金淋巴瘤(NHL)是常见的恶性肿瘤之一。抗CD20单克隆抗体的出现大大提高了复发或难治性CD20阳性B细胞淋巴瘤的缓解率和生存时间。我们运用抗CD20单克隆抗体联合化疗及自体造血干细胞移植治疗2例滤泡细胞性B细胞恶性淋巴瘤患者,现报道如下。     

流式细胞术检测外周血T淋巴细胞亚群在NHL中的意义研究

目的应用流式细胞术检测非霍奇金淋巴瘤（NHL）患者外周血T淋巴细胞亚群绝对值计数并分析其临床意义。方法采集NHL组（n=62）与正常对照组（n=30）空腹外周血2ml,采用流式细胞术检测外周血T淋巴细胞各亚群包括CD3＋、CD4＋、CD8＋细胞的绝对值计数,并可计算出CD4＋／CD8＋比值;两组数值之间进行比较。结果与对照组相比,NHL组CD3＋、CD4＋细胞数明显降低[CD3＋细胞数（823．3±211．5）、CD4＋细胞数（423．8±234．8）]（P〈0．05）,CD8＋细胞数（861．2±634．1）升高（P〈0．05）,CD4＋／CD8＋降低（0．5±0．3）（P〈0．05）。结论NHL患者细胞免疫功能下降,应用流式细胞术进行外周血T淋巴细胞亚群绝对值计数的检测对NHL的诊断、治疗和预后判断有意义。     

Roche申请MabThera的附加适应症

Roche公司在欧盟为它的非何杰金淋巴瘤（NHL）治疗药Mab Thera（rituximab）申请附加适应症,用于先前未经治疗的晚期滤泡性淋巴瘤病人的维持治疗。Rituximab是一种靶向B细胞的抗CD20单克隆抗体,与化疗联用被视为NHL的标准一线治疗药。     

Ten years of rituximab in NHL

Background: Rituximab, a chimeric mouse/human monoclonal antibody targeting the pan-B-cell antigenic marker CD20, was the first monoclonal antibody licensed for use in the treatment of cancer. Objective: This review focuses on the impact of rituximab in the treatment of patients with B-cell non-Hodgkin lymphoma (NHL). Methods: Three key areas related to the use of rituximab in B-cell NHL are discussed: mechanism of action, clinical efficacy in both indolent and aggressive disease, and safety of its use as both monotherapy and in combination with chemotherapy. Results/conclusions: Rituximab has demonstrated significant clinical efficacy in the treatment of NHL, particularly in combination with chemotherapy, and its use has revolutionized the treatment of both indolent and aggressive B-cell NHL over the past decade. Furthermore, consistent toxicity data have been obtained with a safe and tolerable profile in most patients.     

Rituximab in B-cell disorders other than non-Hodgkin's lymphoma

Rituximab is a human/mouse chimeric monoclonal antibody that binds to the CD20 antigen and is expressed at all stages of B-cell development. Rituximab has demonstrated efficacy as monotherapy and in combination with chemotherapy in the treatment of both indolent and aggressive non-Hodgkin's lymphoma (NHL). Rituximab treatment results in rapid depletion of B-cells and this has led to the consideration of other B-cell disorders as candidates for rituximab therapy. Recent studies have demonstrated the efficacy of rituximab in a variety of such disorders, including chronic lymphocytic leukemia (CLL), post-transplant lymphoproliferative disorder (PTLD), Waldenstr?m's macroglobulinemia (WM), multiple myeloma (MM), idiopathic thrombocytopenic purpura (ITP), hairy-cell leukemia (HCL) and cold agglutinin disease (CAD). In patients with CLL, increasing the dose and/or frequency of rituximab treatment has given improved response rates compared with the standard dose schedule used in NHL, and combination immunochemotherapy has yielded an overall response rate of 92% (with a 60% complete response rate). Clinical trials have also demonstrated evidence of efficacy for rituximab in PTLD, WM and relapsed or refractory ITP. Efficacy of rituximab in CAD and relapsed or refractory HCL has also been demonstrated in small studies and case reports. Available data thus indicate that rituximab can be an effective therapy in a wide range of CD20+ lymphoid disorders.     

利妥昔单抗治疗类风湿关节炎的临床研究进展

利妥昔单抗是一种特异性针对CD20分子的基因工程抗体,能与B淋巴细胞表面的CD20结合,并通过补体介导的细胞毒作用等机制对B淋巴细胞进行特异性清除,从而达到治疗作用.利妥昔单抗最初作为抗淋巴瘤药物首先获得美国FDA认证,近年来被应用于类风湿关节炎等自身免疫病的治疗,取得了较好的疗效.现对其治疗类风湿关节炎的作用机制、临床应用和研究进展做一综述.     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents. The latter was a randomised comparison of eight cycles of CHOP plus rituximab 375 mg/m(2) intravenously (one dose per cycle) versus CHOP alone in previously untreated elderly patients (60 to 80 years of age) with diffuse large B-cell lymphoma. In this pivotal trial, 2-year event-free and overall survival were significantly higher with rituximab plus CHOP, and there was no increase in clinically significant adverse effects compared with CHOP alone. Treatment with rituximab is generally well tolerated, particularly in terms of adverse haematological effects and serious or opportunistic infections relative to standard chemotherapy. Infusion-related reactions occur in the majority of patients treated with rituximab; these are usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions. In approximately 10% of patients, however, severe infusion-related reactions develop (e.g. bronchospasm, hypotension). These reactions are usually reversible with appropriate interventions and supportive care but there have been rare reports of fatalities. CONCLUSIONS: Clinical trials with rituximab indicate that the drug has broad application to B-cell malignancies, although further clarification is needed to determine its optimal use in many of these clinical settings. Importantly, rituximab in combination with CHOP chemotherapy has emerged as a new treatment standard for previously untreated diffuse large B-cell lymphoma, at least in elderly patients. Compared with conventional chemotherapy, rituximab is associated with markedly reduced haematological events such as severe neutropenia, as well as associated infections. Rituximab may be particularly suitable for elderly patients or those with poor performance status, and its tolerability profile facilitates its use in combination with cytotoxic drugs. PHARMACODYNAMIC PROPERTIES: Rituximab is a mouse/human chimaeric IgG(1)-kappa monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B lymphocytes. Although treatment with rituximab induces lymphopenia in most patients, typically lasting about 6 months, a full recovery of B lymphocytes in the peripheral blood is usually seen 9-12 months after therapy, as CD20 is not expressed on haematopoietic stem cells. CD20 is, however, expressed on >90% of B-cell non-Hodgkin's lymphomas (NHL) and to a lesser degree on B-cell chronic lymphocytic leukaemia (CLL) cells.Although not fully elucidated, the cytotoxic effects of rituximab on CD20-positive malignant B cells appears to involve complement-dependent cytotoxicity, complement-dependent cellular cytotoxicity, antibody-dependent cellular cytotoxicity and induction of apoptosis. In addition, in vitro data indicate that rituximab sensitises tumour cells to the effects of conventional chemotherapeutic drugs. PHARMACOKINETIC PROPERTIES: Serum rituximab concentrations increased in proportion to dose across a wide range of single- and multiple-dose intravenous regimens in patients with B-cell NHL. When administll NHL. When administered at a dose of 375 mg/m(2) once weekly for 4 weeks in a pivotal trial in patients with relapsed or refractory indolent B-cell NHL (follicular or small lymphocytic subtypes), peak serum concentrations essentially doubled from the first (239.1 mg/L) to the fourth (460.7 mg/L) infusion, while elimination half-life (t(1/2)) increased from 76.3 to 205.8 hours (3.2 to 8.6 days). The concomitant increase in serum rituximab concentrations and t(1/2) with each successive infusion may be due, at least in part, to the elimination of circulating CD20-positive B cells and reduction or saturation of CD20-binding sites after the initial infusions of rituximab. The pharmacokinetic properties of rituximab are also characterised by wide inter-individual variability, and serum drug concentrations that are correlated with clinical response. Although pharmacokinetic data are limited in patients with aggressive forms of NHL, such as diffuse large B-cell lymphoma, rituximab appears to have a similar pharmacokinetic profile in these patients to that in patients with indolent B-cell NHL. The pharmacokinetics of rituximab are also reported to be similar whether the drug is administered with or without cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. THERAPEUTIC USE: A number of studies have demonstrated efficacy of intravenous rituximab in patients with various lymphoid malignancies of B-cell origin, including indolent (e.g. follicular lymphoma) and aggressive (e.g. diffuse large B-cell lymphoma) forms of NHL, and CLL, but the drug has not yet been approved for use in CLL, and approved indications in NHL vary between countries. In the US, for example, rituximab is available for the treatment of patients with low-grade or follicular, relapsed or refractory, CD20-positive B-cell NHL. In Europe, the drug has similar approval for relapsed or refractory follicular NHL as in the US, but has also been approved for use in combination with CHOP chemotherapy for the most common aggressive form of NHL (CD20-positive, diffuse large B-cell lymphoma). Rituximab was approved for these indications primarily on the basis of results from two pivotal trials. In Japan, rituximab has been approved for indolent B-cell NHL and mantle cell lymphoma (an aggressive form of B-cell NHL), primarily on the basis of results of a Japanese phase II trial. Indolent NHL: Results of several studies evaluating rituximab 375 mg/m(2) once weekly for 4 weeks in patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic lymphomas) showed objective response (OR) rates ranging from approximately 40-60% in those receiving the drug for relapsed or refractory indolent B-cell NHL, and slightly higher (50-70%) for those receiving rituximab as first-line therapy. In a pivotal trial in 166 patients with relapsed or refractory low-grade or follicular B-cell NHL, intent-to-treat (ITT) analysis showed an OR rate of 48%, and a projected median time to progression of 13 months.Encouraging data are also emerging on the use of rituximab in combination with chemotherapeutic agents (e.g. CHOP, fludarabine-containing regimens) or other drugs (e.g. interferon-alpha2a) in previously untreated patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic subtypes). Rates for OR were consistently around 95%, with the majority being complete responses (CRs). Follow-up data from a study in 40 patients with low-grade or follicular B-cell NHL treated with rituximab plus CHOP as first-line therapy showed that responses were durable with a progression-free survival and median duration of response >5 years.Bcl-2 gene rearrangement (t14;18) occurs in malignant cells in up to 85% of patients with follicular lymphoma, and minimal residual disease in peripheral blood and bone marrow can be monitored using polymerase chain reaction (PCR). In several studies assessing blood and/or bone marrow, rituximab has achieved molecular response (conversion from PCR-positive to PCR-negative bcl-2 status) in at least half of the patients. Aggressive NHL: Studies with rituximab as monotherapy in aggressive B-cell NHL, a potentially curable disorder, have generally been restricted to patients with relapsed or recurrent disease, since CHOP has traditionally been the standard first-line treatment regimen. However, promising results from phase II monotherapy studies prompted further clinical investigation of rituximab in conjunction with chemotherapy. Thus, most studies with rituximab in patients with aggressive forms of B-cell NHL have involved combination therapy, including a pivotal randomised trial comparing eight cycles of standard CHOP therapy plus rituximab 375 mg/m(2) (one dose per cycle) versus CHOP alone in 399 previously untreated elderly patients (60-80 years of age) with diffuse large B-cell lymphoma. Results of the pivotal trial showed a clear advantage for rituximab plus CHOP versus CHOP in terms of event-free survival (primary endpoint) at 2 years (57% vs 38%, p < 0.001). Overall survival at 2 years (70% vs 57%, p < 0.01) and CR rate (76% vs 63%, p < 0.01) were also higher with the rituximab-CHOP combination. Other, smaller trials with rituximab in combination with CHOP or other chemotherapeutic regimens, either as first-line therapy or for patients with relapsed or refractory aggressive B-cell NHL, have also shown promising results in terms of clinical response rates.CLL: In relatively small trials (n < 40) conducted primarily in patients with relapsed or refractory B-cell CLL, rituximab monotherapy (various regimens) achieved OR rates of 23-45%, with median duration of response ranging from approximately 3-10 months. (ABSTRACT TRUNCATED)     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab (MabThera, Rituxan) is an anti-CD20 monoclonal antibody that induces lysis and apoptosis of normal and malignant human B cells, and sensitises malignant B cells to the cytotoxic effect of chemotherapy. In phase III trials in patients with indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL), intravenous rituximab in combination with chemotherapy was more effective as first- or second-line therapy than chemotherapy alone in providing tumour remission and patient survival. Likewise, in patients with chronic lymphocytic leukaemia (CLL), rituximab in combination with chemotherapy appeared more effective than chemotherapy alone as either first- or second-line treatment. In addition, rituximab maintenance therapy was shown to significantly prolong tumour remission and patient survival in patients with indolent B-cell NHL or CLL. The combination of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was cost effective as first-line therapy for advanced-stage diffuse large B-cell NHL compared with CHOP alone. Rituximab, either alone or in combination with chemotherapy, was generally well tolerated in patients with NHL or CLL. Overall, rituximab in combination with chemotherapy, is a valuable option for first- and second-line therapy in patients with advanced-stage indolent or aggressive B-cell NHL, and possibly those with B-cell CLL, and is included in current treatment guidelines for these indications. The drug is also potentially useful as maintenance therapy in patients with indolent B-cell NHL or CLL.     

Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20)

B cells play a central role in the pathogenesis of SLE. Not only do they make autoantibodies, but they can provide immunoregulatory controls of T cells, dendritic cells, and other B cells, in part through cytokine production. The availability of a chimeric monoclonal antibody that targets B cells has made it possible to treat SLE by B-cell depletion. Rituximab binds to the B-cell specific antigen CD20, and depletes B cells from the peripheral blood and lymphoid tissues. A growing number of anecdotal series and case reports suggest that rituximab may provide clinical benefit in SLE with acceptable toxicity, although the variability in responses of individual patients is not yet fully understood. Two large ongoing randomized controlled trials will determine the efficacy of rituximab in SLE, both renal and extra-renal, and will inform us better about the biology of the B cell in this disease and the effects of B-cell depletion.     

Rituximab

Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule on the B-cell surface. It is the first antibody of its kind to be licensed for the treatment of non-Hodgkin's lymphoma. Rituximab was found to be effective, well-tolerated and has a good safety profile, though its precise cellular effects are still not well understood. Rituximab has been shown to be of therapeutic benefit in various autoimmune diseases in which B lymphocytes play a role. This article summarizes the current literature regarding the use of rituximab in lymphoma, rheumatoid arthritis, systemic lupus erythematosus and other selected autoimmune diseases.     

Dermatologic rituximab dosing: treatment of refractory pemphigus vulgaris in an adolescent male

Rituximab is a chimeric monoclonal antibody against CD20 that mediates B-cell depletion. It has been shown to be effective in a variety of autoimmune-related diseases, including pemphigus vulgaris. Most reports of pemphigus treatment utilize the weekly dosing regimen designed for the treatment of B-cell malignancy. The authors report a case of successful treatment of refractory pemphigus vulgaris in an adolescent male using three infusions of rituximab spread over a four-month period of time. The authors also discuss recent updates in rituximab's mechanism of action in autoimmune disease. Rituximab acts to destroy auto-reactive B-cells prior to their development into auto-antibody producing plasma cells. More recent reports have shown that rituximab also indirectly leads to a decrease of autoreactive CD4+ T cells via depletion of B-cells that are necessary for antigen presentation. Monthly to bi-monthly rituximab infusion dosing may be a more appropriate dosing strategy for autoimmune disease that minimizes potential side effects while generating remission of disease. Dermatology continues to see an increase in use of medications designed for treatment of rheumatologic disease and malignancy. Additional studies should focus on the appropriate dosing of these medications for dermatologic conditions that limit the risk of adverse effects while preserving therapeutic benefit.     

Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritis

Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years. B cells are now known to have multiple key roles in the pathogenesis of RA. Data is now available that indicates efficacy and safety of B-cell depletion with rituximab in the treatment of RA in a variety of patient groups. The clinical outcomes from these studies, together with its safety profile, have led to rituximab being licensed for the treatment of patients with RA who have failed to obtain benefit from anti-TNF-alpha agents.