Inova Center for Personalized Health, Inova Schar Cancer Institute, 3225 Gallows Rd, 7th Floor, Tower D, Fairfax, VA, 22031, USA.
Inova Center for Personalized Health, Inova Schar Cancer Institute, 8505 Arlington Blvd Suite 140, Fairfax, VA, 22031, USA.
J Immunother Cancer. 2018 Jun 5;6(1):49. doi: 10.1186/s40425-018-0365-3.
Hemophagocytic Lymphohistiocytosis (HLH), a rare but potentially fatal syndrome of immune hyperactivation, may be an under-recognized immune-related adverse event (irAE). Unlike other irAEs, HLH triggered by immune checkpoint blockade is not well described; no particular diagnostic guidelines and treatment regimens exist. The HLH-2004 criteria remain as the common diagnostic guide. For the treatment of HLH, various combinations of chemotherapeutic, immunosuppressive and glucocorticoid agents are used.
We report a case of HLH in a 58-year-old metastatic melanoma patient who was undergoing immune checkpoint blockade with pembrolizumab, a programmed cell death-1 (PD-1) receptor inhibitor. The patient presented with fever, upper normal sized spleen, anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, reduced NK cell activity and elevated sCD163 levels, fulfilling the Histiocyte Society HLH-2004 diagnostic criteria. Our patient was successfully treated with oral prednisone (1 mg/kilogram/day), suggesting that HLH from immune checkpoint inhibitors may respond to steroids alone.
Early diagnosis and treatment of HLH are critical to avoid progressive tissue damage, organ failure and possibly death. HLH should be suspected in clinical presentations with fever, cytopenias and hyperinflammatory markers. HLH in the setting of immune checkpoint blockade may be treated with steroids only but further evidence is required.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见但潜在致命的免疫过度激活综合征，可能是一种未被充分认识的免疫相关不良事件（irAE）。与其他 irAE 不同，免疫检查点抑制剂诱发的 HLH 尚未得到充分描述；目前尚无特定的诊断指南和治疗方案。HLH-2004 标准仍然是常见的诊断指南。对于 HLH 的治疗，通常采用化疗、免疫抑制和糖皮质激素药物的各种组合。
我们报告了一例 58 岁转移性黑色素瘤患者在接受派姆单抗（一种程序性死亡受体-1 [PD-1] 抑制剂）免疫检查点抑制剂治疗时发生 HLH 的病例。该患者表现为发热、中上正常大小的脾脏、贫血、血小板减少、高甘油三酯血症、高铁蛋白血症、NK 细胞活性降低和 sCD163 水平升高，符合组织细胞协会 HLH-2004 诊断标准。我们的患者成功接受了口服泼尼松（1 毫克/千克/天）治疗，这表明免疫检查点抑制剂引起的 HLH 可能仅对类固醇有反应。
早期诊断和治疗 HLH 对于避免进行性组织损伤、器官衰竭和死亡至关重要。当出现发热、细胞减少和炎症标志物升高时，应怀疑 HLH。免疫检查点抑制剂相关 HLH 可能仅用类固醇治疗即可，但需要更多证据。
