Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis:: A single-center report of 48 patients
Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis:: A single-center report of 48 patients
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DOI：
10.1542/peds.2005-1789
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发表时间：
2006-04-01
期刊：
影响因子：
8
通讯作者：
Fischer, A
中科院分区：
文献类型：
--
作者：
Ouachée-Chardin, M;Elie, C;Fischer, A
目标.家族性噬血细胞性淋巴组织细胞增生症（FHLH）是一种遗传决定的疾病，其特征为早发性发热、肝脾肿大、中枢神经系统疾病、血小板减少症、凝血功能障碍和噬血细胞增多症。它是由损害T细胞介导的和天然细胞毒性的遗传缺陷引起的。基于化疗或免疫治疗的治疗可以达到缓解。造血干细胞移植（HSCT），然而，是唯一的治疗选择，但最佳的方式和长期的结果还不清楚。我们回顾性分析了1982年至2004年在一个中心连续治疗的48例FHLH患者的HSCT结果。总生存率为58.5%，中位随访时间为5.8年，并延长至20年。活动性疾病和单倍体相合HSCT的组合具有不良预后，因为在这种情况下，HLH疾病更频繁地与移植失败相关。12例患者因移植失败（n = 7）或继发性移植物丢失导致HLH复发（n = 5）接受了2次移植。移植相关毒性主要包括静脉闭塞性疾病，发生在28%的移植中，与年轻、单倍体相合移植和预处理方案中使用抗胸腺细胞球蛋白（ATG）有关。所有白细胞供体嵌合率>= 20%的患者均获得持续缓解。长期后遗症是有限的，因为28例患者中只有2例（7%）发生了轻度神经功能障碍。这项调查证明了HSCT作为FHLH治疗的长期疗效。HSCT维持生活质量。这表明，HSCT应尽早进行完全缓解已经实现。需要进一步的研究来改进程序并减少其毒性作用。
OBJECTIVES. Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetically determined disorder characterized by the early onset of fever, hepatosplenomegaly, central nervous system disease, thrombocytopenia, coagulation disorders, and hemophagocytosis. It is caused by genetic defects that impair T cell-mediated and natural cytotoxicity. Chemotherapy- or immunotherapy-based treatments can achieve remission. Hematopoietic stem cell transplantation (HSCT), however, is the only curative option, but optimal modalities and long-term outcome are not yet well known.METHODS. We retrospectively analyzed the outcome of HSCT that was performed in 48 consecutive patients who had FHLH and were treated in a single center between 1982 and 2004.RESULTS. The overall survival was 58.5% with a median follow-up of 5.8 years and extending to 20 years. A combination of active disease and haploidentical HSCT had a poor prognosis because in this situation, HLH disease is more frequently associated with graft failure. Twelve patients received 2 transplants because of graft failure (n = 7) or secondary graft loss that led to HLH relapse (n = 5). Transplant-related toxicity essentially consisted in veno-occlusive disease, which occurred in 28% of transplants and was associated with young age, haploidentical transplantation, and the use of antithymocyte globulin (ATG) in the conditioning regimen. A sustained remission was achieved in all patients with a donor chimerism >= 20% of leukocytes. Long-term sequelae were limited, because only 2 (7%) of 28 patients experienced a mild neurologic disorder.CONCLUSIONS. This survey demonstrates the long-term efficacy of HSCT as a cure of FHLH. HSCT preserves quality of life. It shows that HSCT should be performed as early as a complete remission has been achieved. Additional studies are required to improve the procedure and reduce its toxic effects.