Schmidt Lindsay A, Lim Megan S
Department of Pathology, M5240 Medical Science I, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109-0602 USA.
J Hematop. 2009 Jul;2(2):121-6. doi: 10.1007/s12308-009-0029-9. Epub 2009 Mar 18.
The enhanced risk of development of lymphoproliferative disorders in patients with inflammatory bowel disease has been attributed to immunosuppressive/immunomodulatory therapies. Infliximab is a chimeric monoclonal immunoglobulin G1 antibody directed against tumor necrosis factor alpha (TNF-α) that was approved by the Food and Drug Administration (FDA) in 1998 as an effective therapeutic agent against inflammatory bowel disease. Malignant lymphomas of both B and T cell lineage have been described in patients undergoing therapy involving TNF-α blockade. To date, eight cases of Epstein-Barr virus (EBV)-negative hepatosplenic T cell lymphoma associated with infliximab have been reported to the FDA's Adverse Event Reporting System, as well as several other T cell lymphoproliferative disorders with aggressive clinical outcomes. We present the histologic, immunophenotypic, and molecular features of a T cell lymphoproliferative disorder involving the axillary lymph node of a 33-year-old male following infliximab treatment for ulcerative colitis. These EBV-negative lymphomas suggest that lymphoproliferative disorders following infliximab treatment for inflammatory bowel disease may involve EBV-independent immune dysregulation. The spectrum of lymphoproliferative disorders associated with infliximab and the potential mechanisms by which they occur are discussed.
炎症性肠病患者发生淋巴增殖性疾病的风险增加，这归因于免疫抑制/免疫调节疗法。英夫利昔单抗是一种嵌合单克隆免疫球蛋白G1抗体，可靶向肿瘤坏死因子α（TNF-α），于1998年被美国食品药品监督管理局（FDA）批准为治疗炎症性肠病的有效药物。在接受TNF-α阻断治疗的患者中，已发现B细胞和T细胞系的恶性淋巴瘤。迄今为止，已有8例与英夫利昔单抗相关的爱泼斯坦-巴尔病毒（EBV）阴性肝脾T细胞淋巴瘤报告给了FDA不良事件报告系统，以及其他一些具有侵袭性临床结局的T细胞淋巴增殖性疾病。我们展示了一名33岁男性在接受英夫利昔单抗治疗溃疡性结肠炎后，腋窝淋巴结发生的T细胞淋巴增殖性疾病的组织学、免疫表型和分子特征。这些EBV阴性淋巴瘤表明，英夫利昔单抗治疗炎症性肠病后的淋巴增殖性疾病可能涉及不依赖EBV的免疫失调。本文讨论了与英夫利昔单抗相关的淋巴增殖性疾病谱及其发生的潜在机制。
