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Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.
Journal of Clinical Immunology ( IF 7.2 ) Pub Date : 2021-07-29 , DOI: 10.1007/s10875-021-01098-0
Hasan Hashem 1 , Giorgia Bucciol 2, 3 , Seza Ozen 4, 5 , Sule Unal 6 , Ikbal Ok Bozkaya 7 , Nurten Akarsu 8 , Mervi Taskinen 9 , Minna Koskenvuo 10 , Janna Saarela 11, 12 , Dimana Dimitrova 13 , Dennis D Hickstein 14 , Amy P Hsu 15 , Steven M Holland 15 , Robert Krance 16 , Ghadir Sasa 16 , Ashish R Kumar 17, 18 , Ingo Müller 19 , Monica Abreu de Sousa 19 , Selket Delafontaine 2, 3 , Leen Moens 3 , Florian Babor 20 , Federica Barzaghi 21 , Maria Pia Cicalese 22 , Robbert Bredius 23 , Joris van Montfrans 24 , Valentina Baretta 25 , Simone Cesaro 25 , Polina Stepensky 26 , Neven Benedicte 27 , Despina Moshous 27 , Guillaume Le Guenno 28 , David Boutboul 29 , Jignesh Dalal 30 , Joel P Brooks 31 , Elif Dokmeci 32 , Jasmeen Dara 33 , Carrie L Lucas 31 , Sophie Hambleton 34 , Keith Wilson 35 , Stephen Jolles 36 , Yener Koc 37 , Tayfun Güngör 38 , Caroline Schnider 39 , Fabio Candotti 40 , Sandra Steinmann 41 , Ansgar Schulz 41 , Chip Chambers 42 , Michael Hershfield 43 , Amanda Ombrello 44 , Jennifer A Kanakry 13 , Isabelle Meyts 2, 3
Affiliation  

PURPOSE Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. METHODS We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). RESULTS Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. CONCLUSION HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. CLINICAL IMPLICATIONS HCT is a definitive cure for DADA2 with > 95% survival.

中文翻译:


造血细胞移植治愈腺苷脱氨酶 2 缺乏症:30 名患者的报告。



目的 腺苷脱氨酶 2 (DADA2) 缺乏是一种遗传性先天性免疫缺陷,其特征为自身炎症(反复发热)、血管病变(葡萄状青斑、结节性多动脉炎、腔隙性缺血性中风和颅内出血)、免疫缺陷、淋巴细胞增殖、免疫性血细胞减少和骨髓衰竭(BMF)。肿瘤坏死因子 (TNF-α) 阻断是血管病变的首选治疗方法,但通常无法逆转难治性血细胞减少症。我们的目的是研究 DADA2 患者的造血细胞移植 (HCT) 的结果。方法 我们对 DADA2 患者的 HCT 结果进行了回顾性研究。主要结局是总生存期(OS)。结果 来自 12 个国家的 30 名 DADA2 患者总共接受了 38 次 HCT。 HCT 的适应症是 BMF、免疫性血细胞减少、恶性肿瘤或免疫缺陷。 HCT 的中位年龄为 9 岁(范围:2-28 岁)。最终移植的预处理方案为清髓性(n = 20)、降低强度(n = 8)或非清髓性(n = 2)。供体为 HLA 匹配相关 (n = 4)、HLA 匹配无关 (n = 16)、HLA 单倍体相合 (n = 2) 或 HLA 不匹配无关 (n = 8)。中位随访 2 年(范围:0.5-16 年)后,2 年 OS 为 97%,2 年无 GvHD 无复发生存率为 73%。血液学和免疫学表型得到解决,并且没有新的血管事件。 16/17 名测试患者的血浆 ADA2 酶活性恢复正常。六名患者需要不止一次 HCT。结论 HCT 是 DADA2 的有效治疗方法,成功逆转了难治性血细胞减少症以及血管病变和免疫缺陷。临床意义 HCT 是 DADA2 的最终治愈方法,存活率 > 95%。
更新日期:2021-07-29
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