Tsilifis Christo, Raedler Johannes, Renke Joanna, Medinger Michael, Laberko Alexandra, Haraldsson Ásgeir, Patel Niraj, Ciznar Peter, Wong Melanie, Keogh Steven J, Gray Paul, Mitchell Richard, Bigley Venetia, Elcombe Suzanne, Hauck Fabian, Albert Michael H, Tholouli Eleni, Herwadkar Archana, Elkhalifa Shuayb, Kosmidis Chris, Callisti Giorgio, Burroughs Lauri M, Chen Karin, Carpenter Ben, Fox Thomas A, Morris Emma C, Uppuluri Ramya, Raj Revathi, Yanagimachi Masakatsu, Buddingh Emilie P, Oikonomopoulou Christina, Gonzalez Corina, Dimitrova Dimana, Kanakry Jennifer A, Arnold Danielle, Pai Sung-Yun, Slatter Mary A, Pearce Mark S, Worth Austen, Freeman Alexandra F, Gennery Andrew R
Paediatric Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Blood Adv. 2025 Aug 26;9(16):4126-4135. doi: 10.1182/bloodadvances.2025016158.
Signal transduction and activator of transcription 3 hyperimmunoglobulin E syndrome (STAT3-HIES) is a multisystem disorder causing recurrent skin and respiratory infection with bronchiectasis, pneumatoceles, and aspergillosis; lymphoma; and extraimmune manifestations including fractures and vasculopathy. Published data on immune and extraimmune hematopoietic stem cell transplant (HSCT) outcomes focus on case reports or small cohorts. We conducted an international multicenter retrospective study of HSCT in STAT3-HIES. Primary end points were overall survival (OS) and event-free survival (EFS; events were death, graft failure, chronic graft-versus-host disease [GVHD]). We identified 41 patients over a 28-year period. HSCT indication was infection (93%) or lymphoma (7%). Median age at HSCT was 14 years (range, 4-45). Most patients had pre-HSCT respiratory disease (93%), including parenchymal lung disease (68%), and prior suspected/confirmed pulmonary fungal infection (32%). Patients received peripheral blood stem cells (51%) or marrow (49%) from HLA 10/10-matched unrelated donors (44%), matched family donors (44%), mismatched family donors (10%), or 1 9/10-mismatched unrelated donor (2%). Conditioning regimens were predominantly treosulfan-based (59%; with thiotepa, 34%); other patients received busulfan-based (24%) or melphalan-based (17%) regimens. Median follow-up for surviving patients was 5 years (0.8-28). The 5-year OS was 93%, and 5-year EFS 90%. Cumulative incidence of grade 2 to 4 acute GVHD was 22%. Median whole blood donor chimerism at latest follow-up was 100%. Eighty-seven percent of patients have reduced or no bacterial or fungal respiratory infection. After HSCT, 20% developed new skeletal fractures. This worldwide study expanded data on HSCT for STAT3-HIES to 41 patients; despite significant pre-HSCT pulmonary morbidity, OS was high, and patients have improved skin and respiratory disease though the impact on extraimmune manifestations appears limited.
信号转导与转录激活因子3高免疫球蛋白E综合征（STAT3-HIES）是一种多系统疾病，可导致反复的皮肤和呼吸道感染，并伴有支气管扩张、肺气囊和曲霉病；淋巴瘤；以及包括骨折和血管病变在内的免疫外表现。已发表的关于免疫和免疫外造血干细胞移植（HSCT）结果的数据主要集中在病例报告或小队列研究中。我们对STAT3-HIES患者的HSCT进行了一项国际多中心回顾性研究。主要终点是总生存期（OS）和无事件生存期（EFS；事件定义为死亡、移植失败、慢性移植物抗宿主病[GVHD]）。我们在28年的时间里确定了41例患者。HSCT的适应证为感染（93%）或淋巴瘤（7%）。HSCT时的中位年龄为14岁（范围4-45岁）。大多数患者在HSCT前患有呼吸系统疾病（93%），包括实质性肺病（68%），以及先前疑似/确诊的肺部真菌感染（32%）。患者接受了来自10/10 HLA匹配的无关供者（44%）、匹配的家族供者（44%）、不匹配的家族供者（10%）或1个9/10 HLA不匹配的无关供者（2%）的外周血干细胞（51%）或骨髓（49%）。预处理方案主要是以曲奥舒凡为基础的（59%；联合噻替派，34%）；其他患者接受以白消安为基础的（24%）或美法仑为基础的（17%）方案。存活患者的中位随访时间为5年（0.8-28年）。5年总生存率为93%，5年无事件生存率为90%。2至4级急性GVHD的累积发生率为22%。最新随访时全血供者嵌合率的中位数为100%。87%的患者细菌或真菌性呼吸道感染减少或消失。HSCT后，20%的患者出现了新的骨骼骨折。这项全球研究将STAT3-HIES患者HSCT的数据扩展至41例；尽管HSCT前肺部发病率较高，但总生存率较高，患者的皮肤和呼吸系统疾病有所改善，不过对免疫外表现的影响似乎有限。
