Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.

Adult Hematology Necker Enfants Malades University Hospital Assistance Publique Hôpitaux de Paris Paris France

Biotherapy Department and Clinical Investigation Center Assistance Publique Hôpitaux de Paris Paris France

Bone Marrow Transplant Department Great Ormond Street Hospital For Sick Children London England

Bone Marrow Transplantation Unit National Institute of Children's Diseases Bratislava Slovakia

CEREDIH SCETIDE Necker Enfants Malades University Hospital Assistance Publique Hôpitaux de Paris Paris France

Clinical Department of Paediatric Bone Marrow Transplantation Oncology and Haematology Wroclaw Medical University Wroclaw Poland

Department for Children and Adolescent Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Hematopoietic Stem Cell Transplantation Dmitriy Rogachev National Center for Pediatric Hematology Oncology and Immunology Moscow Russian Federation

Department of Pediatric Hematology and Oncology Comenius University Bratislava Slovakia

Department of Pediatric Hematology and Oncology University Hospital Motol Prague Czech Republic

Department of Pediatric Hematoloy Oncology Cell and Gene Therapy Bambino Gesù Children's Hospital Sapienza University Rome Italy

Department of Pediatric Hematoloy Oncology Cell and Gene Therapy University Medical Center University Utrecht Utrecht The Netherlands

Department of Pediatrics BMT Unit Hacettepe University Faculty of Medicine Ankara Turkey

Department of Pediatrics Dr von Hauner Children's Hospital University Hospital Ludwig Maximilians Universität München Munich Germany

Department of Pediatrics Karolinska University Hospital Huddinge Clintec Karolinska Institutet Stockholm Sweden

Department of Pediatrics Pediatric Stem Cell Transplantation Program Willem Alexander Children's Hospital Leiden University Medical Center The Netherlands

Department of Pediatrics University Medical Center Ulm Ulm Germany

Division of Pediatric Stem Cell Therapy Department of Pediatric Oncology Hematology and Clinical Immunology Medical Faculty Heinrich Heine University Düsseldorf Germany

Hematology Oncology Immunology Gene Therapy and Stem Cell Transplantation University Children's Hospital Zurich Eleonore Foundation and Children's Research Center Zürich Switzerland

IMAGINE Institute Université de Paris Sorbonne Paris Cité Paris France

Necker Enfants Malades University Hospital Assistance Publique Hôpitaux de Paris Paris France

Paediatric Stem Cell Transplant Unit Great North Children's Hospital Newcastle upon Tyne United Kingdom

Pediatric Hematology and Oncology MHH Hannover Germany

Pediatric Hematology CHU Lille Lille France

Pediatric Hematology Oncology Akdeniz University School of Medicine Antalya Turkey

Pediatric Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy

Pediatric Immunohematology IRCCS Ospedale San Raffaele Milan Italy

Pediatric Immunology Hematology and Rheumatology Department Necker Enfants Malades University Hospital Assistance Publique Hôpitaux de Paris Paris France

Pediatric Oncohaematology and BMT Children's Hospital Brescia Italy

Princess Máxima Center Utrecht The Netherlands

RM Gorbacheva Research Institute Pavlov University St Petersburg Russian Federation

Scientific Department Belarusian Research Center for Pediatric Oncology Hematology and Immunology Borovlyany Minsk Region Belarus

Statistical and Study Unit EBMT office Leiden The Netherlands

Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne United Kingdom

University College London GOS Institute of Child Health London England; and

Vita Salute San Raffaele University Milan Italy

Blood. 2022 Mar 31;139(13):1935-1936. doi: 10.1182/blood.2022015612. PubMed

Citace poskytuje Crossref.org

Treosulfan vs busulfan conditioning for allogeneic bmt in children with nonmalignant disease: a randomized phase 2 trial