High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease.
High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease.
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造血干细胞移植治疗慢性肉芽肿病后自身免疫性疾病的高发病率。
DOI：
10.1016/j.bbmt.2018.03.029
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Ome
中科院分区：
文献类型：
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作者：
Yanir,AsafD;Hanson,ImeldaC;Shearer,WilliamT;Noroski,LenoraM;Forbes,LisaR;Seeborg,FelizO;Nicholas,Sarah;Chinn,Ivan;Orange,JordanS;Rider,NicholasL;Leung,KathrynS;Naik,Swati;Carrum,George;Sasa,Ghadir;Hegde,Meenakshi;Ome
造血干细胞移植（HSCT）在慢性肉芽肿病（CGD）患者中的作用和方法缺乏共识。对这些患者进行HSCT后的长期随访对于了解其潜在并发症并决定谁将从HSCT中获益最大是至关重要的。我们报告了24例CGD患者的HSCT和长期随访结果，这些患者在12年期间（2003年至2015年）从相关（n = 6）或不相关（n = 18）供体中移植，在准备方案中使用高剂量Alemtuzumab。我们评估了不良事件的发生率和时间以及潜在的风险因素。我们详细描述了CGD患者HSCT后自身免疫增强的新发现。中位随访1460天，22例患者为完全供体嵌合体，2例患者为稳定的混合嵌合体。所有可评估患者的中性粒细胞氧化爆发试验均正常化。无患者发生II级至IV级急性移植物抗宿主病，无患者发生慢性移植物抗宿主病。24例患者中有12例发生了17种自身免疫性疾病（AD）。重度AD（血细胞减少症和神经病）仅发生在无关供体环境中，主要发生在HSCT后第一年，而甲状腺AD也发生在相关供体环境中，并且发生在HSCT后3年以上。两名患者死于感染并发症后发展自身免疫性血细胞减少症。另有一名患者严重脑损伤。其余21例患者的长期Lansky评分≥ 80。来自无关供体的HSCT的结果与相关供体相当，但可能增加发生重度AD的风险。较低剂量的Alemtuzumab可能会降低这种风险，应在进一步的研究中进行测试。
There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.