Rituximab-associated acute thrombocytopenia: An under-diagnosed phenomenon
Rituximab-associated acute thrombocytopenia: An under-diagnosed phenomenon
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DOI：
10.1002/ajh.21372
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发表时间：
2009-04-01
影响因子：
12.8
通讯作者：
Raanani, Pia
中科院分区：
文献类型：
--
作者：
Ram, Ron;Bonstein, Lilach;Raanani, Pia
急性输液反应是利妥昔单抗最常见的记录不良反应，明显的细胞因子释放综合征和血液学不良反应要罕见得多。描述了一例套细胞淋巴瘤患者的临床过程，他在使用利妥昔单抗后出现急性血小板减少和白细胞减少，并回顾了文献。利妥昔单抗给药2天后，用双抗体夹心法测定血清补体和血清中三种细胞因子--肿瘤坏死因子-α、白介素6、白介素1的水平。抗血小板药物依赖性抗体的鉴定采用两种方法：流式细胞术免疫荧光试验和血小板抗原单抗固定(MAIPA)。血清肿瘤坏死因子-α水平较正常显著升高，而IL-6、IL-1水平无明显升高。流式细胞术和MAIPA法均未能检测到抗血小板的利妥昔单抗依赖抗体。补体水平较正常降低。文献检索得到10篇关于另外15名患者的报道。最常见的淋巴瘤类型为套细胞淋巴瘤，6例累及骨髓，10例脾肿大。在10例患者中，急性细胞减少先于细胞因子释放综合征或输液相关症状。通常，血小板减少与出血症状无关。血小板减少症是最常见的急性细胞减少症。推测的发病机制与细胞因子释放综合征和补体激活有关。具有潜在危险因素的患者，如脾肿大和骨髓受累，出现与细胞因子释放综合征相适应的临床表现，应密切监测利妥昔单抗相关性细胞减少症。上午好。J.血醇。84：247-250,2009。(C)2009年Wiley-Liss，Inc.
Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines-TNF-alpha, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia. Am. J. Hematol. 84:247-250, 2009. (C) 2009 Wiley-Liss, Inc.