Pegoraro Francesco, Chinnici Aurora, Beneforti Linda, Tanturli Michele, Trambusti Irene, De Fusco Carmela, Micalizzi Concetta, Barat Veronica, Cesaro Simone, Gaspari Stefania, Dell'Acqua Fabiola, Todesco Alessandra, Timeus Fabio, Aricò Maurizio, Favre Claudio, Tondo Annalisa, Coniglio Maria Luisa, Sieni Elena, Working Group Aieop Histiocytosis
Department of Health Sciences, University of Florence, Florence, Italy; Pediatric Hematology Oncology, Meyer Children's Hospital IRCCS, Florence.
Pediatric Hematology Oncology, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence.
Haematologica. 2024 Aug 1;109(8):2515-2524. doi: 10.3324/haematol.2023.283893.
Primary hemophagocytic lymphohistiocytosis (pHLH) is a severe, life-threatening hyperinflammatory syndrome caused by defects in genes of the granule-dependent cytotoxic pathway. Here we investigated the clinical presentation and outcome in a large cohort of 143 patients with pHLH diagnosed in the last 15 years and enrolled in the Italian registry. The median age at diagnosis was 12 months (interquartile range, 2-81), and 92 patients (64%) fulfilled the HLH-2004 criteria. Of 111 patients who received first-line combined therapy (HLH-94, HLH-2004, Euro-HIT protocols), 65 (59%) achieved complete response and 21 (19%) partial response. Thereafter, 33 patients (30%) reactivated, and 92 (64%) received hematopoietic stem cell transplantation, 78 of whom (85%) survived and were alive at a median follow-up from diagnosis of 67 months. Thirty-six patients (25%) died before hematopoietic stem cell transplantation and 14 (10%) after. Overall, 93 patients (65%) were alive after a median follow-up of 30 months. Unadjusted predictors of non-response were age <6 months and high ferritin and bilirubin levels, while predictors of pre-transplant and overall mortality were high ferritin and bilirubin levels. At multivariable analysis, high levels of ferritin predicted non-response, while high levels of bilirubin predicted pre-transplant and overall mortality. Despite recent advances in therapeutic management, pHLH remains a life-threatening condition with significant early mortality. Liver dysfunction is the main predictor of poor prognosis.
原发性噬血细胞性淋巴组织细胞增生症（pHLH）是一种由颗粒依赖性细胞毒性途径基因缺陷引起的严重、危及生命的高炎症综合征。在此，我们调查了过去15年中诊断出的143例pHLH患者的临床表现和预后情况，这些患者均被纳入意大利登记系统。诊断时的中位年龄为12个月（四分位间距为2 - 81个月），92例患者（64%）符合HLH - 2004标准。在111例接受一线联合治疗（HLH - 94、HLH - 2004、欧洲噬血细胞性淋巴组织细胞增生症治疗方案）的患者中，65例（59%）实现完全缓解，21例（19%）部分缓解。此后，33例患者（30%）复发，92例（64%）接受了造血干细胞移植，其中78例（85%）存活，在自诊断后的中位随访67个月时仍存活。36例患者（25%）在造血干细胞移植前死亡，14例（10%）在移植后死亡。总体而言，在中位随访30个月后，93例患者（65%）存活。无反应的未调整预测因素为年龄<6个月以及铁蛋白和胆红素水平高，而移植前和总体死亡率的预测因素为铁蛋白和胆红素水平高。在多变量分析中，铁蛋白水平高预测无反应，而胆红素水平高预测移植前和总体死亡率。尽管在治疗管理方面最近取得了进展，但pHLH仍然是一种危及生命的疾病，早期死亡率很高。肝功能障碍是预后不良的主要预测因素。
