https://orcid.org/0000-0002-1368-104X
Key Points
Allogeneic HSCT offers improved infection-free survival despite significant pre-transplant morbidity in patients with STAT3-HIES
Extra-immune disease manifestations such as skeletal disease may not be improved by transplantation.
STAT3 hyper-IgE syndrome (STAT3-HIES) is a multisystem disorder causing recurrent skin and respiratory infection with bronchiectasis, pneumatocoeles, and aspergillosis; lymphoma; and extra-immune manifestations including fractures and vasculopathy. Published data on immune and extra-immune HSCT outcomes focus on case reports or small cohorts. International multicentre retrospective study of HSCT in STAT3-HIES. Primary endpoints were overall survival (OS) and event-free survival (EFS; events were death, graft failure, chronic GvHD). We identified 41 patients over a 28-year period. HSCT indication was infection (93%) or lymphoma (7%). Median age at HSCT was 14 (4-45) years. 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 cell (51%) or marrow (49%) from HLA 10/10-MUD (44%), MFD (44%), MMFD (10%), or one 9/10 MMUD (2%). Median CD34+ stem cell dose was 6.2 (0.05-22.0) cells x106/kg. 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 (0.8-28) years. 5-year OS was 93% and 5-year EFS 90%. Cumulative incidence of grade II-IV acute GvHD was 22%. Median whole blood donor chimerism at latest follow up was 100%. 87% of patients have reduced or no bacterial or fungal respiratory infection. Post-HSCT, 20% developed new skeletal fractures. This worldwide study expand 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 extra-immune manifestations appears limited.
