Department of Women's and Children's Health, Childhood Cancer Research Unit, Karolinska Institutet, Stockholm, Sweden.
Astrid Lindgrens Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Blood. 2024 Jan 18;143(3):233-242. doi: 10.1182/blood.2023020715.
We evaluated malignancy-associated hemophagocytic lymphohistiocytosis (mal-HLH) in Sweden regarding population-based incidence, clinical features, and survival. From 1997 to 2018, we identified 307 adults (≥18 years old) and 9 children (209 males, 107 females; P < .001) with both an HLH-related diagnosis and malignant disease, corresponding to 0.19 per 100 000 adults annually (0.15/100 000 for the entire population), increasing from 0.026 (1997-2007) to 0.34 (2008-2018) (P < .001). In the latest 7-year period (2012-2018), the annual incidence was 0.45 per 100 000 adults (n = 246). This incidence varied between the 6 health care regions in Sweden, from 0.18 to 0.71 (Region Stockholm) per 100 000 adults annually (P < .001), likely due to variable awareness. Mal-HLH was reported in 0.6% of all hematological malignancies, with the highest proportion (2.5%) in young males. Among the 316 patients, the 1-month probability of survival, likely representing the HLH episode, increased significantly from 52% (95% confidence interval [CI], 40-63) (1997-2007) to 71% (95% CI, 65-76) (2008-2018), whereas 2-year survival remained poor (25%; 95% CI, 20-30). Altogether, 52% were lymphomas, 29% leukemias, 8% other hematological malignancies, and 11% solid tumors. Males were more affected than females by mal-HLH, also taking the over-representation of males with hematological malignancies into account (P = .0012). Validation by medical-file reviews revealed 13% over-reporting of HLH. We conclude that the annual mal-HLH incidence has increased 10-fold and was at least 0.71 per 100 000 adults from 2012 to 2018, that is, 0.62 per 100 000 adults considering 13% estimated HLH over-reporting, and that early survival improved significantly, likely due to increased awareness and more HLH-directed therapy.
我们评估了瑞典人群中与恶性肿瘤相关的噬血细胞性淋巴组织细胞增生症（mal-HLH）的发病率、临床特征和生存率。1997 年至 2018 年，我们共发现 307 例成年患者（≥18 岁）和 9 例儿童患者（209 例男性，107 例女性；P<.001）存在噬血细胞性淋巴组织细胞增生症相关诊断和恶性肿瘤，发病率分别为每年每 10 万人中 0.19 例（总人口中为 0.15/100000），呈逐渐上升趋势，从 0.026（1997-2007 年）增至 0.34（2008-2018 年）（P<.001）。在最近的 7 年（2012-2018 年）中，成年患者的发病率为每年每 10 万人中 0.45 例（n=246）。瑞典 6 个医疗保健区的发病率不同，每年每 10 万人中为 0.18-0.71 例（斯德哥尔摩地区）（P<.001），这可能与认识度不同有关。恶性肿瘤相关性噬血细胞性淋巴组织细胞增生症占所有血液系统恶性肿瘤的 0.6%，年轻男性中的比例最高（2.5%）。在 316 例患者中，1 个月生存率（可能代表噬血细胞性淋巴组织细胞增生症发作）显著增加，从 1997-2007 年的 52%（95%可信区间[CI]，40-63）增至 2008-2018 年的 71%（95%CI，65-76）（P<.001），但 2 年生存率仍较差（25%；95%CI，20-30）。总体而言，52%为淋巴瘤，29%为白血病，8%为其他血液系统恶性肿瘤，11%为实体肿瘤。男性受恶性肿瘤相关性噬血细胞性淋巴组织细胞增生症的影响大于女性，这也考虑到了男性血液系统恶性肿瘤的比例过高（P=.0012）。通过病历审查进行验证发现，噬血细胞性淋巴组织细胞增生症的报告率过高 13%。我们得出结论，恶性肿瘤相关性噬血细胞性淋巴组织细胞增生症的年发病率增加了 10 倍，2012 年至 2018 年期间，发病率至少为每 10 万人 0.71 例，考虑到估计的噬血细胞性淋巴组织细胞增生症报告率过高 13%，则发病率为每 10 万人 0.62 例，且早期生存率显著提高，这可能与认识度提高和更多针对噬血细胞性淋巴组织细胞增生症的治疗有关。
