Henter Jan-Inge, Samuelsson-Horne AnnaCarin, Aricò Maurizio, Egeler R Maarten, Elinder Göran, Filipovich Alexandra H, Gadner Helmut, Imashuku Shinsaku, Komp Diane, Ladisch Stephan, Webb David, Janka Gritta
Childhood Cancer Research Unit, Karolinska Institutet, Department of Pediatric Hematology and Oncology, Karolinska Hospital, Stockholm, Sweden.
Blood. 2002 Oct 1;100(7):2367-73. doi: 10.1182/blood-2002-01-0172.
Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n = 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n = 65), died prior to BMT (n = 25), or were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved.
噬血细胞性淋巴组织细胞增生症（HLH）包括家族性（原发性）噬血细胞性淋巴组织细胞增生症（FHL）和继发性HLH（SHLH），二者临床特征均为发热、肝脾肿大和血细胞减少。FHL是一种常染色体隐性疾病，若不治疗往往致命，与凋亡触发缺陷和细胞毒性活性降低有关，导致T淋巴细胞和活化巨噬细胞广泛积聚。1994年，组织细胞协会发起了一项前瞻性国际协作治疗研究（HLH-94），旨在提高生存率。该研究联合了化疗和免疫疗法（依托泊苷、皮质类固醇、环孢素A，以及在部分患者中使用鞘内甲氨蝶呤），随后对持续性、复发性和/或家族性疾病患者进行骨髓移植（BMT）。1994年7月1日至1998年6月30日期间，来自21个国家的113名年龄不超过15岁的符合条件患者开始参与HLH-94研究。所有患者均有患病的兄弟姐妹（n = 25）和/或符合组织细胞协会的诊断标准。中位随访3.1年时，总体估计3年生存率为55%（95%置信区间±9%），家族性病例为51%（±20%）。20名入组儿童存活且未接受治疗超过12个月，未进行BMT。对于接受移植的患者（n = 65）、在BMT前死亡的患者（n = 25）或仍在接受治疗的患者（n = 3），3年生存率为45%（±10%）。BMT后的3年生存率为62%（±12%）。HLH-94非常有效，使大多数患者能够接受BMT。HLH患儿的生存率有了显著提高。
