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Lookup NU author(s): Dr Laura JardineORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 American Society of HematologyThe 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.
Author(s): Hakkarainen M, Sicre de Fontbrune F, Kaaja I, Douglas S, Dalle J-H, Risitano AM, Kulasekararaj A, Alsultan A, Cutler C, Ho VT, Hellstrom-Lindberg E, Mielke S, Myhre AE, Rihani R, Shanap MA, Hashem H, Shimamura A, Rowe RG, Auer F, Beier F, Desnica L, Hough R, Ali Jafri SR, Ayas M, Jardine L, Mellid EF, Corrales I, Richardson D, Ozbek NY, Zaniewska-Tekieli A, Gozdzik J, Ryhanen S, Niinimaki R, Jahnukainen K, Salmenniemi U, Kilpivaara O, Wartiovaara-Kautto U
Publication type: Article
Publication status: Published
Journal: Blood Advances
Year: 2026
Volume: 10
Issue: 7
Pages: 2525-2537
Print publication date: 14/04/2026
Online publication date: 02/02/2026
Acceptance date: 07/01/2026
Date deposited: 21/04/2026
ISSN (print): 2473-9529
ISSN (electronic): 2473-9537
Publisher: American Society of Hematology
URL: https://doi.org/10.1182/bloodadvances.2025018349
DOI: 10.1182/bloodadvances.2025018349
PubMed id: 41628318
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