Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors
Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors
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DOI：
10.1182/blood.v90.12.4743.4743_4743_4748
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发表时间：
1997-12-15
期刊：
影响因子：
20.3
通讯作者：
Fischer, A
中科院分区：
文献类型：
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作者：
Jabado, N;deGraeffMeeder, ER;Fischer, A
家族性噬血细胞淋巴组织细胞增多症(FHL)是一种罕见的遗传性疾病，与生命早期T淋巴细胞和巨噬细胞的过度激活有关，总是导致死亡。来自人类白细胞抗原相合的亲属供者的异基因骨髓移植(BM)是治疗这种疾病的首选方法。然而，只有不到20%的患者有无疾病的人类白细胞抗原相合兄弟姐妹。来自非相合血缘关系供者的骨髓移植之前遇到了很差的结果，移植排斥反应在所有病例中都是主要障碍。我们描述了在14个连续的FHL病例中，来自两个中心的非相合血缘供者(n=13)和来自匹配的非血缘关系供者(n=1)的骨髓移植。10例患者于骨髓移植前病情缓解。为了尽量减少移植物抗宿主病(GVHD)，骨髓中的T细胞被耗尽。在骨髓移植前和骨髓移植后注射针对白细胞功能相关抗原-1(LFA-1，CD11a)cu链和CD2分子的抗黏附抗体，以帮助预防移植排斥反应，并给予白花丹(BU)、环磷酰胺[CP]、依托泊苷(VP16)或抗胸腺细胞球蛋白(ATG)。17例移植中有11例获得持续植入(3例患者有2例移植)，9例患者无病存活，随访期为8至69个月(平均331例)。未观察到大于I期的急性移植物抗宿主病，1例轻度皮肤慢性移植物抗宿主病缓解。骨髓移植过程的毒性很低。使用该方案获得的结果在植入和小样本范围内的无事件存活方面是有希望的。我们的结论是，对于缺乏合适的HLA基因相合供者的FHL患者，免疫学方法用于获得疾病缓解的药物，以及在来自不同基因的供者的T细胞耗尽的骨髓移植中包括抗黏附分子的预处理方案，是值得进一步研究的替代疗法。(C)1997年由美国血液病学会主办。
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BM) from an HLA-identical related donor is the treatment of choice in patients with this disease. However, fewer than 20% of patients have a disease-free HLA-identical sibling. BMT from HLA-nonidentical related donors has previously met with poor results, with graft rejection a major obstacle in all cases. We describe BMTs from HLA-nonidentical related donors (n = 13) and from a matched unrelated donor (n = 1) performed in two centers in 14 consecutive cases of FHL. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell-depleted to minimize graft-versus-host disease (GVHD). Antiadhesion antibodies specific for the cu chain of the leukocyte function-associated antigen-1 (LFA-1, CD11a) and the CD2 molecules were infused pre-BMT and post-BMT to help prevent graft rejection, in addition to a conditioning regimen of busulfan (BU), cyclophosphamide [CP], end etoposide (VP16) or antithymocyte globulin (ATG). Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-up period of 8 to 69 months (mean, 331. Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-free survival within the limitations of the small sample. We conclude that an immunologic approach in terms of drugs used to obtain disease remission and a conditioning regimen that includes antiadhesion molecules in T-cell-depleted BMT from HLA genetically nonidentical donors is an alternative treatment that warrants further study in FHL patients who lack a suitable HLA genetically identical donor. (C) 1997 by The American Society of Hematology.