Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency
Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency
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DOI：
10.1182/blood-2011-06-365049
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发表时间：
2011-09-29
期刊：
影响因子：
20.3
通讯作者：
Hickstein, Dennis D.
中科院分区：
文献类型：
--
作者：
Cuellar-Rodriguez, Jennifer;Gea-Banacloche, Juan;Hickstein, Dennis D.
我们对 6 名患有新描述的遗传性免疫缺陷综合征的患者进行了非清髓性 HSCT，该综合征是由 GATA2 突变引起的，这种疾病的特征是非结核分枝杆菌感染、单核细胞减少、B 细胞和 NK 细胞缺乏，并有转化为骨髓增生异常综合征/急性髓性白血病的倾向。两名患者接受了来自匹配相关捐献者的外周血干细胞 (PBSC)，2 名患者接受了来自匹配无关捐献者的 PBSC，2 名患者接受了来自脐带血 (UCB) 捐献者的干细胞。匹配相关和无关捐赠者的接受者接受氟达拉滨和 200 cGy 全身照射 (TBI)； UCB 接受者除了氟达拉滨和 TBI 之外还接受环磷酰胺作为调理。所有患者在移植后均接受他克莫司和西罗莫司治疗。中位随访时间为 17.4 个月（范围 10-25），5 名患者仍存活。所有患者在移植前缺陷的造血室中均实现了高水平的供体植入。不良事件包括单 UCB 移植受者的延迟植入、4 名患者的 GVHD 以及双 UCB 移植受者的免疫介导的全血细胞减少症和肾病综合征。 GATA2 缺陷的非清髓性 HSCT 会导致严重缺陷的单核细胞、B 细胞和 NK 细胞群的重建以及临床表型的逆转。在 www.clinicaltrials.gov 上注册为 NCT00923364。 （血。2011；118（13）：3715-3720）
We performed nonmyeloablative HSCT in 6 patients with a newly described genetic immunodeficiency syndrome caused by mutations in GATA2-a disease characterized by nontuberculous mycobacterial infection, monocytopenia, B- and NK-cell deficiency, and the propensity to transform to myelodysplastic syndrome/acute myelogenous leukemia. Two patients received peripheral blood stem cells (PBSCs) from matched-related donors, 2 received PBSCs from matched-unrelated donors, and 2 received stem cells from umbilical cord blood (UCB) donors. Recipients of matched-related and -unrelated donors received fludarabine and 200 cGy of total body irradiation (TBI); UCB recipients received cyclophosphamide in addition to fludarabine and TBI as conditioning. All patients received tacrolimus and sirolimus posttransplantation. Five patients were alive at a median follow-up of 17.4 months (range, 10-25). All patients achieved high levels of donor engraftment in the hematopoietic compartments that were deficient pretransplantation. Adverse events consisted of delayed engraftment in the recipient of a single UCB, GVHD in 4 patients, and immune-mediated pancytopenia and nephrotic syndrome in the recipient of a double UCB transplantation. Nonmyeloablative HSCT in GATA2 deficiency results in reconstitution of the severely deficient monocyte, B-cell, and NK-cell populations and reversal of the clinical phenotype. Registered at www.clinicaltrials.gov as NCT00923364. (Blood. 2011; 118(13):3715-3720)