Mahlaoui Nizar, Ouachée-Chardin Marie, de Saint Basile Geneviève, Neven Bénédicte, Picard Capucine, Blanche Stéphane, Fischer Alain
Unité d'Immunologie et Hématologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Pediatrics. 2007 Sep;120(3):e622-8. doi: 10.1542/peds.2006-3164. Epub 2007 Aug 14.
Familial hemophagocytic lymphohistiocytosis is a genetically determined condition that is characterized by unremitting CD8 T lymphocyte and macrophage activation and leads to death in the absence of therapy. On the basis of the immunologic pathophysiology of familial hemophagocytic lymphohistiocytosis, we propose a therapy with a combination of antithymocyte globulins with corticosteroids, cyclosporin A, and intrathecal injections of methotrexate.
We retrospectively analyzed the outcome of antithymocyte globulin-based therapy that was performed in 38 consecutive patients who had familial hemophagocytic lymphohistiocytosis and were treated in a single center between 1991 and 2005. Overall, they received 45 courses of antithymocyte globulin (5-10 mg/kg per day for 5 days).
This regimen was associated with infections after 10 of 45 courses of antithymocyte globulin. There were 6 events after 11 antithymocyte globulin courses given as second-line therapy against 4 after 34 antithymocyte globulin courses in patients who were treated primarily with antithymocyte globulin. Antithymocyte globulin administration led to rapid and complete response of familial hemophagocytic lymphohistiocytosis in 73% of cases, partial response in 24%, and no response only once. When hematopoietic stem cell transplantation was performed early after complete or partial response induction, it led to a high rate of cure, in 16 of 19 cases. Overall survival was 21 of 38 with 4 toxic deaths.
Antithymocyte globulin based immunotherapy of familial hemophagocytic lymphohistiocytosis is efficient and carries an acceptable toxicity when used as a first treatment of familial hemophagocytic lymphohistiocytosis.
家族性噬血细胞性淋巴组织细胞增生症是一种由基因决定的疾病，其特征为CD8 T淋巴细胞和巨噬细胞持续激活，若不接受治疗会导致死亡。基于家族性噬血细胞性淋巴组织细胞增生症的免疫病理生理学，我们提出了一种联合使用抗胸腺细胞球蛋白、皮质类固醇、环孢素A及鞘内注射甲氨蝶呤的治疗方法。
我们回顾性分析了1991年至2005年间在单一中心接受治疗的38例家族性噬血细胞性淋巴组织细胞增生症患者接受基于抗胸腺细胞球蛋白治疗的结果。总体而言，他们共接受了45个疗程的抗胸腺细胞球蛋白治疗（每天5 - 10 mg/kg，共5天）。
在45个疗程的抗胸腺细胞球蛋白治疗中有10个疗程出现感染。作为二线治疗给予11个疗程抗胸腺细胞球蛋白治疗后出现6例感染事件，而在主要接受抗胸腺细胞球蛋白治疗的患者中，34个疗程抗胸腺细胞球蛋白治疗后出现4例感染事件。抗胸腺细胞球蛋白治疗使73%的家族性噬血细胞性淋巴组织细胞增生症病例迅速且完全缓解，24%部分缓解，仅1例无反应。在诱导完全或部分缓解后早期进行造血干细胞移植，19例中有16例治愈率很高。38例患者中21例总体存活，4例死于毒性反应。
基于抗胸腺细胞球蛋白的家族性噬血细胞性淋巴组织细胞增生症免疫疗法有效，作为家族性噬血细胞性淋巴组织细胞增生症的一线治疗时，其毒性是可接受的。
