Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study
Abstract: 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 an...
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Elsevier
2025-08-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925003441 |
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| author | Christo Tsilifis Johannes Raedler Joanna Renke Michael Medinger Alexandra Laberko Ásgeir Haraldsson Niraj Patel Peter Ciznar Melanie Wong Steven J. Keogh Paul Gray Richard Mitchell Venetia Bigley Suzanne Elcombe Fabian Hauck Michael H. Albert Eleni Tholouli Archana Herwadkar Shuayb Elkhalifa Chris Kosmidis Giorgio Callisti Lauri M. Burroughs Karin Chen Ben Carpenter Thomas A. Fox Emma C. Morris Ramya Uppuluri Revathi Raj Masakatsu Yanagimachi Emilie P. Buddingh Christina Oikonomopoulou Corina Gonzalez Dimana Dimitrova Jennifer A. Kanakry Danielle Arnold Sung-Yun Pai Mary A. Slatter Mark S. Pearce Austen Worth Alexandra F. Freeman Andrew R. Gennery |
| author_facet | Christo Tsilifis Johannes Raedler Joanna Renke Michael Medinger Alexandra Laberko Ásgeir Haraldsson Niraj Patel Peter Ciznar Melanie Wong Steven J. Keogh Paul Gray Richard Mitchell Venetia Bigley Suzanne Elcombe Fabian Hauck Michael H. Albert Eleni Tholouli Archana Herwadkar Shuayb Elkhalifa Chris Kosmidis Giorgio Callisti Lauri M. Burroughs Karin Chen Ben Carpenter Thomas A. Fox Emma C. Morris Ramya Uppuluri Revathi Raj Masakatsu Yanagimachi Emilie P. Buddingh Christina Oikonomopoulou Corina Gonzalez Dimana Dimitrova Jennifer A. Kanakry Danielle Arnold Sung-Yun Pai Mary A. Slatter Mark S. Pearce Austen Worth Alexandra F. Freeman Andrew R. Gennery |
| author_sort | Christo Tsilifis |
| collection | DOAJ |
| description | Abstract: 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. |
| format | Article |
| id | doaj-art-ff8e675c03ec4f8296a34d31ff28ca8a |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-ff8e675c03ec4f8296a34d31ff28ca8a2025-08-20T03:41:57ZengElsevierBlood Advances2473-95292025-08-019164126413510.1182/bloodadvances.2025016158Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide studyChristo Tsilifis0Johannes Raedler1Joanna Renke2Michael Medinger3Alexandra Laberko4Ásgeir Haraldsson5Niraj Patel6Peter Ciznar7Melanie Wong8Steven J. Keogh9Paul Gray10Richard Mitchell11Venetia Bigley12Suzanne Elcombe13Fabian Hauck14Michael H. Albert15Eleni Tholouli16Archana Herwadkar17Shuayb Elkhalifa18Chris Kosmidis19Giorgio Callisti20Lauri M. Burroughs21Karin Chen22Ben Carpenter23Thomas A. Fox24Emma C. Morris25Ramya Uppuluri26Revathi Raj27Masakatsu Yanagimachi28Emilie P. Buddingh29Christina Oikonomopoulou30Corina Gonzalez31Dimana Dimitrova32Jennifer A. Kanakry33Danielle Arnold34Sung-Yun Pai35Mary A. Slatter36Mark S. Pearce37Austen Worth38Alexandra F. Freeman39Andrew R. Gennery40Paediatric 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; Correspondence: Christo Tsilifis, Paediatric Haematopoietic Stem Cell Transplant Unit, Great North Children’s Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 3QX, United Kingdom;Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilian University Munich, Munich, GermanyDepartment of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland; Outdoor Department of Clinical Immunology for Children, University Clinical Centre, Gdańsk, PolandDepartment of Hematology, University Hospital Basel, Basel, SwitzerlandDepartment of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, RussiaChildren’s Hospital Iceland, Landspitali – University Hospital, Reykjavík, IcelandDivision of Allergy and Immunology, Department of Pediatrics, Duke University, Durham, NCPediatric Department, Comenius University Medical Faculty, National Institute of Children's Diseases, Bratislava, SlovakiaAllergy and Immunology, Children’s Hospital at Westmead, Westmead, NSW, AustraliaCancer Centre for Children, Children’s Hospital at Westmead, Westmead, NSW, AustraliaAllergy and Immunology, Sydney Children’s Hospital, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Sydney, NSW, AustraliaKids Cancer Centre, Sydney Children’s Hospital, Randwick, NSW, Australia; School of Women & Children’s Health, University of New South Wales, Sydney, NSW, AustraliaTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Northern Centre for Bone Marrow Transplantation, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United KingdomDepartment of Immunology, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United KingdomDepartment of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilian University Munich, Munich, GermanyDepartment of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilian University Munich, Munich, GermanyDepartment of Haematology, Manchester Royal Infirmary, Manchester, United KingdomDepartment of Clinical Immunology, Salford Care Organisation, Northern Care Alliance NHS Trust, Salford, United KingdomCentre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; Allergy and Immunology Division, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab EmiratesNational Aspergillosis Centre, Manchester University NHS Foundation Trust, Manchester, United KingdomInfectious Diseases Department, Manchester University NHS Foundation Trust, Manchester, United KingdomFred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington, Seattle Children’s Hospital, Seattle, WADivision of Immunology, Department of Pediatrics, University of Washington and Seattle Children’s Research Institute, Seattle, WAUniversity College London Institute of Immunity and Transplantation, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United KingdomUniversity College London Institute of Immunity and Transplantation, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United KingdomUniversity College London Institute of Immunity and Transplantation, University College London, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Department of Immunology, Royal Free London Hospitals NHS Foundation Trust, London, United KingdomPaediatric Haemato-Oncology, Apollo Hospitals, Chennai, IndiaPaediatric Haemato-Oncology, Apollo Hospitals, Chennai, IndiaDepartment of Pediatrics, Yokohama City University, Yokohama, Japan; Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, JapanPediatric Stem Cell Transplantation Program, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The NetherlandsStem Cell Transplant Unit, Aghia Sofia Children’s Hospital, Athens, GreeceImmune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MDCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MDCenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MDImmune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MDImmune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MDPaediatric 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 KingdomPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United KingdomDepartment of Immunology and Gene Therapy, Great Ormond Street Hospital for Children, London, United KingdomLaboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MDPaediatric 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 KingdomAbstract: 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.http://www.sciencedirect.com/science/article/pii/S2473952925003441 |
| spellingShingle | Christo Tsilifis Johannes Raedler Joanna Renke Michael Medinger Alexandra Laberko Ásgeir Haraldsson Niraj Patel Peter Ciznar Melanie Wong Steven J. Keogh Paul Gray Richard Mitchell Venetia Bigley Suzanne Elcombe Fabian Hauck Michael H. Albert Eleni Tholouli Archana Herwadkar Shuayb Elkhalifa Chris Kosmidis Giorgio Callisti Lauri M. Burroughs Karin Chen Ben Carpenter Thomas A. Fox Emma C. Morris Ramya Uppuluri Revathi Raj Masakatsu Yanagimachi Emilie P. Buddingh Christina Oikonomopoulou Corina Gonzalez Dimana Dimitrova Jennifer A. Kanakry Danielle Arnold Sung-Yun Pai Mary A. Slatter Mark S. Pearce Austen Worth Alexandra F. Freeman Andrew R. Gennery Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study Blood Advances |
| title | Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study |
| title_full | Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study |
| title_fullStr | Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study |
| title_full_unstemmed | Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study |
| title_short | Allogeneic hematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study |
| title_sort | allogeneic hematopoietic stem cell transplantation for stat3 hyper ige syndrome a worldwide study |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925003441 |
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