Complete atrioventricular block induced by rituximab in monotherapy in an aged patient with non-Hodgkin’s diffuse large B-cell lymphoma

Rituximab is a treatment option to non-Hodg kin's diffuse large B-cell lymphoma (NHDLBCL) in advanced stage and comorbility. It is known the cardiotoxicity effect of this drug, but there is no previous report describing a complete atrioventricular block (CAVB) secundary to treatment with Rituximab. We present an elderly woman treated with monotherapy with Rituximab who experienced a CAVB after administration of the fifth dose of this drug.     

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.     

Rituximab for sight-threatening refractory pediatric Vogt–Koyanagi–Harada disease

Rituximab was trialed in a refractory Vogt–Koyanagi–Harada disease (VKH). A 10-year-old girl with panuveitis recalcitrant to treatment, including corticosteroids, was diagnosed with VKH 20 months later. Following rituximab at 0, 1, 6, and 18 months, response was favorable after the second dose, usual life activity resumed after the third dose (uveitis was inactivated and vision improved), and eyes stabilized 9 months after the fourth dose. Rituximab is effective in the treatment and long-term control of advanced, pediatric VKH.     

Rituximab in cryoglobulinemic peripheral neuropathy

Type II mixed cryoglobulinemia is sustained by an oligoclonal production of IgM sharing rheumatoid activity and can be associated with renal, cutaneous, rheumatologic or neurological manifestations. Peripheral neuropathy is a major cause of morbidity in hepatitis C virus-associated mixed cryoglobulinemia and is often refractory to any treatment. Rituximab induces a selective depletion of IgM-producing B cells, and both case reports on monoclonal IgM-related polyneuropathy as well as studies on small series of patients with interferon α-resistant mixed cryoglobulinemia have suggested that it may be beneficial. Thirteen patients affected by type II mixed cryoglobulinemia with polyneuropathy were treated. Rituximab was administered intravenously at a dose of 375 mg/m² on days 1, 8, 15 and 22. Two more doses were given 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in the clinical neurological condition, in electromyographic indices and in laboratory parameters (including cryocrit, viral load, complement levels and rheumatoid factor) over at least 12 months. Sensory symptoms disappeared or improved following treatment. A significant improvement in the clinical neuropathy disability score was observed. Electromyography examination revealed that the amplitude of compound motor action potential had increased. Viral load did not significantly change. Side effects were negligible. In this open prospective study, rituximab appeared to be effective and safe in the treatment of patients with type II cryoglobulinemia-associated neuropathy.