a Internal Medicine Department , Regional Hospital of Presidente Prudente, Presidente Prudente , São Paulo , Brazil.
b Infectious Diseases and Immunology Department , Oeste Paulista University, Presidente Prudente , São Paulo , Brazil.
Immunopharmacol Immunotoxicol. 2018 Feb;40(1):13-17. doi: 10.1080/08923973.2017.1392562. Epub 2017 Nov 2.
The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases.
We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL).
Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment.
Seven patients were followed and median age was 56.0 ± 5.0 years (range, 41.9-71.6 years). At baseline, the mean level of IgG was 333.7 ± 40.8 and IgM 40.9 ± 11.3 mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%).
Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.
利妥昔单抗（RTX）的使用正在增加，即使在发展中国家也是如此。它已成为包括 B 细胞淋巴瘤和自身免疫性疾病在内的各种疾病的一线治疗或化疗（CHOP；环磷酰胺、阿霉素、长春新碱和泼尼松）的辅助药物。
我们描述了与非霍奇金淋巴瘤（NHL）患者接受 RTX 治疗相关的传染病和免疫标志物。
在静脉免疫球蛋白（IVIg）给药前后测定血清免疫球蛋白。在接种前后评估肺炎球菌 23 型 IgG 特异性抗肺炎球菌抗体。在治疗过程中进行免疫表型和淋巴细胞增殖测定。
7 例患者接受了随访，中位年龄为 56.0±5.0 岁（范围，41.9-71.6 岁）。基线时，IgG 的平均水平为 333.7±40.8mg/dL，IgM 为 40.9±11.3mg/dL；免疫球蛋白 A 和 E（IgA 和 IgE）低于检测限。两名患者的 B 细胞减少或缺失，五名患者的 T 细胞亚群正常。所有患者对乙型肝炎病毒、破伤风、白喉和 23 价肺炎球菌多糖疫苗均未能产生有效的接种后免疫反应。在 RTX/CHOP 治疗期间，六名患者在反复感染后（85.7%为社区获得性肺炎，85.7%为慢性鼻窦炎，42.9%为胃肠炎）接受了人免疫球蛋白（IVIg）治疗。
对肺炎球菌疫苗反应不良会增加这些患者患呼吸道疾病的易感性。在接受 RTX 治疗的 NHL 患者中，用 IVIg 替代治疗控制复发性传染病所带来的益处至关重要。处理针对癌症治疗的单克隆抗体（尤其是 RTX）的临床医生应意识到，由诱导性低丙种球蛋白血症和呼吸道感染引起的症状风险增加。
