Division of Hematology, University and University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland.
Center of Laboratory Medicine, University Hospital, Inselspital Bern, CH-3010, Bern, Switzerland.
Ann Hematol. 2018 Oct;97(10):1961-1973. doi: 10.1007/s00277-018-3388-4. Epub 2018 Jun 13.
Recently, an immunodeficiency syndrome caused by guanine-adenine-thymine-adenine 2 (GATA2) deficiency has been described. The syndrome is characterized by (i) typical onset in early adulthood, (ii) profound peripheral blood cytopenias of monocytes, B lymphocytes, and NK cells, (iii) distinct susceptibility to disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections (particularly human papillomavirus), and (iv) a high risk of developing hematologic malignancies (myelodysplastic syndromes (MDS); acute myeloid leukemias (AML)). Considerable clinical heterogeneity exists among patients with GATA2 deficiency, but once infectious symptoms occur or MDS/AML arises, survival declines significantly. Allogeneic hematopoietic cell transplantation (HCT) currently provides the only curative treatment option for both MDS/AML and dysfunctional immunity with life-threatening opportunistic infections. Strategies regarding timing of allogeneic HCT, antimicrobial prophylaxis and treatment, intensity of the preparative regimen, and optimal donor and graft source have not been clearly defined due to the rarity of the disease. Here, we provide a comprehensive analysis of the available literature and published case reports on the use of allogeneic HCT in patients with GATA2 deficiency. In addition, a case of a young woman with GATA2 deficiency, who developed an immune reconstitution inflammatory syndrome in her mycobacterial skin lesions post allogeneic HCT is presented and illustrates distinct problems encountered in this disease context.
最近，描述了一种由鸟嘌呤-腺嘌呤-胸腺嘧啶-腺嘌呤 2（GATA2）缺乏引起的免疫缺陷综合征。该综合征的特征为：（i）典型发病于成年早期，（ii）单核细胞、B 淋巴细胞和 NK 细胞的外周血细胞严重减少，（iii）易发生弥散性非结核分枝杆菌（NTM）和其他机会性感染（特别是人乳头瘤病毒），（iv）罹患血液系统恶性肿瘤（骨髓增生异常综合征（MDS）；急性髓系白血病（AML））的风险较高。GATA2 缺乏症患者之间存在相当大的临床异质性，但一旦出现感染症状或 MDS/AML 发生，生存情况显著下降。异基因造血细胞移植（HCT）目前是 MDS/AML 和危及生命的机会性感染所致免疫功能障碍的唯一根治性治疗选择。由于疾病罕见，异基因 HCT 的时机、抗菌预防和治疗、预处理方案的强度以及最佳供体和移植物来源等策略尚未明确界定。在此，我们对 GATA2 缺乏症患者接受异基因 HCT 的可用文献和已发表病例报告进行了全面分析。此外，我们还介绍了一名年轻女性 GATA2 缺乏症患者，她在异基因 HCT 后发生分枝杆菌皮肤病变的免疫重建炎症综合征，并说明了该疾病背景下遇到的独特问题。
