Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, Vancouver, BC, Canada.
Hematology Institute, Meir Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Immunobiology, Cincinnati Children's Medical Center, Cincinnati, OH, USA.
Lancet Haematol. 2022 Mar;9(3):e217-e227. doi: 10.1016/S2352-3026(21)00366-5. Epub 2022 Jan 31.
Haemophagocytic lymphohistiocytosis (HLH) is an inflammatory syndrome that can occur with cancer (malignancy-associated HLH) or with immune-activating therapies for cancer. Patients with lymphoma appear to be at particularly high risk for malignancy-associated HLH. The familial form of HLH is characterised by uncontrolled activation of macrophages and cytotoxic T cells, which can be identified by genetics or specific immune markers. However, the pathophysiology of malignancy-associated HLH is not well understood, and distinguishing pathological immune activation from the laboratory and clinical abnormalities seen in cancer and cancer treatment is challenging. Emerging diagnostic tools, such as serum cytokine or chemokine concentrations, flow cytometry, and other functional measures, are discussed. Mortality remains high with current approaches. Targeted therapy, including blockade of specific cytokines such as IL-1, IL-6, and IFNγ, and inhibition of the JAK-STAT pathways might improve outcomes for some patients. Finally, we discuss a framework for thinking of malignancy-associated HLH within a larger umbrella concept of cytokine storm syndrome.
噬血细胞性淋巴组织细胞增生症（HLH）是一种炎症综合征，可发生于癌症（恶性肿瘤相关 HLH）或癌症的免疫激活治疗中。淋巴瘤患者似乎特别容易发生恶性肿瘤相关 HLH。HLH 的家族形式表现为巨噬细胞和细胞毒性 T 细胞的失控激活，这可以通过遗传学或特定的免疫标志物来识别。然而，恶性肿瘤相关 HLH 的病理生理学尚不清楚，区分癌症和癌症治疗中所见的病理性免疫激活与实验室和临床异常具有挑战性。新兴的诊断工具，如血清细胞因子或趋化因子浓度、流式细胞术和其他功能测量方法，正在讨论中。目前的治疗方法死亡率仍然很高。针对特定细胞因子（如 IL-1、IL-6 和 IFNγ）的靶向治疗，以及 JAK-STAT 通路的抑制，可能会改善某些患者的预后。最后，我们讨论了将恶性肿瘤相关 HLH 纳入细胞因子风暴综合征这一更大概念框架的思路。
