Hematopoietic Stem Cell Transplantation Is a Curative Therapy for Transferrin Receptor 1 (TFRC) Deficiency.
Hematopoietic Stem Cell Transplantation Is a Curative Therapy for Transferrin Receptor 1 (TFRC) Deficiency.
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造血干细胞移植是治疗转铁蛋白受体 1 (TFRC) 缺乏症的一种疗法。
DOI：
10.1016/j.jaip.2020.10.018
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Al-Herz,Waleed
中科院分区：
文献类型：
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作者：
Whangbo,JenniferS;Chou,Janet;Al-Dhekri,Hasan;Harris,Marian;Geha,RaifS;Pai,Sung-Yun;Al-Herz,Waleed
背景转铁蛋白受体1（transferrin receptor 1，TfR 1）基因编码的转铁蛋白受体1（transferrin receptor 1，TfR 1）介导的铁摄取对淋巴细胞的发育和增殖至关重要。人TFRC基因常染色体隐性突变导致以T细胞和B细胞增殖缺陷以及类别转换受损为特征的联合免疫缺陷。在所有报告的病例中，临床表现都很严重，症状包括复发性鼻窦炎感染、低丙种球蛋白血症、慢性腹泻，目的描述异基因造血干细胞移植（HSCT）的结局方法对2011年7月至2018年5月在波士顿儿童医院接受同种异体HSCT的5例TFRC缺陷患者进行回顾性病历回顾性研究。结果间歇性血小板减少症和中性粒细胞减少症是我们队列中临床表现的主要特征，3例在HSCT前接受骨髓评估的患者被发现有骨髓生成障碍和发育不良的体征。1例患者在11岁时接受了移植，发生了与骨髓增生异常综合征有关的克隆性细胞遗传学异常。所有5例患者均耐受清髓性预处理方案，并具有稳健的供体细胞植入，血细胞减少消退，不依赖静脉内免疫球蛋白替代。所有5例患者均存活，平均随访47.1个月移植后（范围，15.7-85.4），没有开发急性或慢性移植物抗宿主病。结论同种异体造血干细胞移植是治疗TFRC缺乏症和抢救所有已知的疾病表现。TFRC缺乏的患者可能有造血细胞恶性转化的倾向，并可能在病程早期从HSCT中获益。
BackgroundIron uptake mediated by transferrin receptor 1 (TfR1), encoded by theTFRCgene, is essential for lymphocyte development and proliferation. Autosomal-recessive mutations in the humanTFRCgene cause a combined immunodeficiency characterized by defective T- and B-cell proliferation as well as impaired class-switching. Clinical presentations have been severe in all reported cases, with symptoms including recurrent sinopulmonary infections, hypogammaglobulinemia, chronic diarrhea, and intermittent cytopenias.ObjectiveTo describe outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients withTFRCdeficiency.MethodsRetrospective chart review study of 5 patients withTFRCdeficiency who underwent allogeneic HSCT between July 2011 and May 2018 at Boston Children's Hospital.ResultsIntermittent thrombocytopenia and neutropenia were a predominant feature of the clinical presentation in our cohort, and 3 patients who underwent bone marrow evaluation before HSCT were found to have signs of dysmyelopoiesis and dysplasia. One patient, who had a transplant at age 11 years, developed a clonal cytogenetic abnormality concerning for myelodysplastic syndrome. All 5 patients tolerated myeloablative conditioning regimens and had robust donor cell engraftment with resolution of cytopenias and independence from intravenous immunoglobulin substitution. All 5 patients were alive at a median follow-up of 47.1 months posttransplant (range, 15.7-85.4) and none had developed acute or chronic graft-versus-host disease.ConclusionsAllogeneic HSCT is curative forTFRCdeficiency and rescues all known disease manifestations. Patients withTFRCdeficiency may have a predisposition to malignant transformation of hematopoietic cells and may benefit from HSCT earlier in their disease course.