Hirst W J, Layton D M, Singh S, Mieli-Vergani G, Chessells J M, Strobel S, Pritchard J
Department of Haematological Medicine, King's College Hospital School of Medicine and Dentistry, London.
Br J Haematol. 1994 Dec;88(4):731-9. doi: 10.1111/j.1365-2141.1994.tb05111.x.
Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of inappropriate macrophage activation. Both familial and sporadic forms, which may be infection-associated, are recognized. Between 1985 and 1991 we treated 23 cases of HLH (12 male, 11 female). There were eight familial cases, defined by a previously affected sibling and/or history of consanguinity, age 3 d to 15 months at presentation. The age of the remaining 15 cases varied from 1 month to 9.5 years. A potential viral trigger was identified in four cases (EBV, two; parvovirus B19, one; echovirus II, one) including one familial case. Six of eight (75%) patients who received supportive care alone, including all four familial cases, died within 6 months of presentation. Both long-term survivors in this group presented at an older age (7.5 and 8 years) and had proven or suspected virus-associated HLH. 15 patients were treated with etoposide (150-250 mg/m2 days 1-3 every 21 d) and methylprednisolone; 10 patients received intrathecal methotrexate in addition. In nine (60%) of these cases a complete (six) or partial (three) response was achieved, though one child suffered a fatal 'tumour lysis' syndrome. Overall mortality in the treated group was 66.6%, being highest (75%) in patients under 2 years at presentation compared to 33% in those over 2 years. Two of three familial and one of five sporadic cases relapsed and died 3 d to 20 months from diagnosis. Only one familial case survives at follow-up of 11 months. Of the five remaining survivors, two received allogeneic bone marrow transplantation (one matched related, one haploidentical) and are alive at 11 and 29 months. Three cases aged 2.5, 7.5 and 9.5 years remain in remission at 11, 20 and 25 months respectively. The high mortality of HLH supports a role for allogeneic BMT in selected cases, particularly those with a familial basis or under 2 years at presentation.
噬血细胞性淋巴组织细胞增生症（HLH）是一种巨噬细胞异常激活的罕见疾病。已确认存在家族性和散发性两种形式，后者可能与感染相关。1985年至1991年间，我们治疗了23例HLH患者（男12例，女11例）。其中有8例家族性病例，根据此前有患病同胞和/或近亲结婚史定义，发病时年龄为3天至15个月。其余15例患者年龄从1个月至9.5岁不等。在4例患者（2例EB病毒感染、1例细小病毒B19感染、1例艾柯病毒II感染）中发现了潜在的病毒触发因素，其中包括1例家族性病例。仅接受支持治疗的8例患者中有6例（75%）死亡，包括所有4例家族性病例，均在发病后6个月内死亡。该组中的2例长期存活者发病时年龄较大（7.5岁和8岁），且已证实或怀疑为病毒相关性HLH。15例患者接受了依托泊苷（150 - 250 mg/m²，第1 - 3天，每21天重复）和甲泼尼龙治疗；10例患者还接受了鞘内注射甲氨蝶呤。在这些病例中，9例（60%）实现了完全缓解（6例）或部分缓解（3例），不过有1名儿童死于致命的“肿瘤溶解”综合征。治疗组的总体死亡率为66.6%，发病时年龄在2岁以下的患者死亡率最高（75%），而2岁以上患者为33%。3例家族性病例中有2例、5例散发性病例中有1例复发，并在诊断后3天至20个月内死亡。在11个月的随访中，仅1例家族性病例存活。其余5例存活者中，2例接受了异基因骨髓移植（1例为配型相合的亲属供体，1例为单倍体相合供体），分别在11个月和29个月时仍存活。3例年龄分别为2.5岁、7.5岁和9.5岁的患者分别在11个月、20个月和25个月时仍处于缓解状态。HLH的高死亡率表明，在某些特定病例中，尤其是家族性病例或发病时年龄在2岁以下的患者，异基因骨髓移植可能具有重要作用。
