Year: 2026
Type: article
Study design: Observational Study
Abstract: ABSTRACT: The hallmark of ERCC6L2 disease (ED) is a highly penetrant progression from bone marrow failure to erythroid-predominant, TP53-mutated myeloid malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplant (HSCT) remains the only potentially curative option, but concerns exist regarding transplant-related toxicities (TRT) due to the underlying DNA repair defect. To the best of our knowledge, this is the first study to report a systematic analysis of HSCT in ED. We conducted a retrospective multicenter study involving 45 patients with ED who underwent HSCT in 2004-2024. The primary outcomes were overall survival (OS), TRT, and nonrelapse mortality (NRM). The 1-year and 3-year OS were 79% (95% confidence interval [CI], 66-91) and 54% (95% CI, 35-73), respectively. Previous history of excess blasts significantly predicted inferior survival (hazard ratio [HR], 6.8; 95% CI, 2.2-20.3; P< .001), with a median survival of 12 months (95% CI, 0-24). Grade 3 to 5 endothelial toxicities occurred in 27% of patients and were associated with higher NRM (HR, 7.7; 95% CI, 1.5-38.8; P = .016). The use of nontreosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared with reduced-intensity conditioning (RIC; HR, 4.9; 95% CI, 1.1-22.0; P = .040), whereas outcomes with treosulfan-based MAC were comparable to RIC. In summary, allogeneic HSCT is a viable curative strategy for ED when performed before transformation to an aggressive malignancy, for example myelodysplasia with excess blasts or acute myeloid leukemia. However, the elevated incidence of endothelial toxicity highlights the importance of optimizing conditioning intensity and enhancing peritransplant monitoring in this population.
Source: Blood Advances
Authors: Marja Hakkarainen, Flore Sicre de Fontbrune, Ilse Kaaja, Suvi Douglas, Jean-Hugues Dalle, Antonio Maria Risitano, Austin Kulasekararaj, Abdulrahman Alsultan, Corey Cutler, Vincent T. Ho, Eva Hellström-Lindberg, Stephan Mielke, Anders E. Myhre, Rawad Rihani, Mayada Abu Shanap, Hasan Hashem, Akiko Shimamura, R. Grant Rowe, Franziska Auer, Fabian Beier, Lana Desnica, Rachael Hough, Syed Rafat Ali Jafri, Mouhab Ayas, Laura Jardine, Eugenia Fernandez Mellid, Irene Corrales, Deborah Richardson, Namik Yasar Özbek, Anna Zaniewska-Tekieli, Jolanta Gozdzik, Samppa Ryhänen, Riitta Niinimäki, Kirsi Jahnukainen, Urpu Salmenniemi, Outi Kilpivaara, Ulla Wartiovaara-Kautto
Institutions: University of Helsinki, Helsinki University Hospital, Hôpital Saint-Louis, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, Groupe Hospitalo-Universitaire Paris Nord, Azienda Ospedaliera S.Giuseppe Moscati, King's College Hospital NHS Foundation Trust, King's College Hospital, King Saud Medical City, King Saud University, Dana-Farber Cancer Institute, Karolinska Institutet, Oslo University Hospital, King Hussein Cancer Center, Harvard University, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Technical University of Munich, RWTH Aachen University, University Hospital Centre Zagreb, University College London Hospitals NHS Foundation Trust, King Faisal Specialist Hospital & Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle University, Complejo Hospitalario Universitario de Santiago, Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Vall d'Hebron Institut de Recerca, Centro de Investigación Biomédica en Red, Banc de Sang i Teixits, University Hospital Southampton NHS Foundation Trust, Sağlık Bilimleri Üniversitesi, Uniwersytecki Szpital Dziecięcy, Jagiellonian University, Helsinki Children's Hospital, Oulu University Hospital, University of Oulu, Finnish Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: Ida Montinin Säätiö, Blood Disease Research Foundation, Helsingin Yliopisto, Suomen Lääketieteen Säätiö, Ministerio de Economía y Competitividad, Biomedicum Helsinki-säätiö, Signe ja Ane Gyllenbergin Säätiö, Sigrid Juséliuksen Säätiö, Syöpäsäätiö, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Medac, National Institutes of Health, Instituto de Salud Carlos III, European Regional Development Fund
Awards: G1080262567, Abordaje de los trastornos hemorrágicos hereditarios de etiología compleja mediante la aplicación de una estrategia común de secuenciación de exomas, Systems Biology of Bone Marrow Failure and MDS for Precision Medicine, G1799144664, Investigación de la etiología molecular no resuelta de los trastornos hemorrágicos hereditarios mediante herramientas moleculares avanzadas y sistemas de integración de datos.
OpenAlex ID: W7127179448