Allogeneic Hematopoietic Stem Cell Transplantation in ERCC6L2 Disease

The hallmark of ERCC6L2 disease (ED) is a highly penetrant progression from bone marrow failure (BMF) to erythroid-predominant, TP53-mutated myeloid malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option, but concerns exist regarding transplant-related toxicities due to the underlying DNA repair defect. 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), transplant-related toxicity, and non-relapse mortality (NRM). The 1-year and 3-year OS were 79% (95% confidence interval [CI], 66-91) and 54% (95% CI, 35-73), respectively. Prior history of excess blasts significantly predicted inferior survival (hazard ratio [HR], 6.8; 95% CI, 2.2-20.3; P<0.001), with a median survival of 12 months (95% CI, 0-24). Grade 3-5 endothelial toxicities occurred in 27% of patients and were associated with higher NRM (HR, 7.7; 95% CI, 1.5-38.8; P=0.016). The use of non-treosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared to reduced-intensity conditioning (RIC) (HR, 4.9; 95% CI, 1.1-22.0; P=0.040), 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 i.e. 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.

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Journal
Blood Advances
Published
2026-02-02
DOI
https://doi.org/10.1182/bloodadvances.2025018349
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Allogeneic Hematopoietic Stem Cell Transplantation in ERCC6L2 Disease

M. Ayas, Anna Zaniewska-Tekieli, Jean‐Hugues Dalle, Ilse Kaaja et al.
Blood Advances
Acute Myeloid Leukemia Research
article

Allogeneic Hematopoietic Stem Cell Transplantation in ERCC6L2 Disease

M. Ayas, Anna Zaniewska-Tekieli, Jean‐Hugues Dalle, Ilse Kaaja, Mayada Abu Shanap, Lana Desnica, Franziska Auer, Rawad Rihani, Riitta Niinimäki, Marja Hakkarainen, A. Shimamura, Irene Corrales Insa, Suvi Douglas, Outi Kilpivaara, Laura Jardine, Eugenia Fernández-Mellid, Hasan A. Hashem, Deborah Richardson, Fabian Beier, Rachael Hough, Stephan Mielke, Anders Eivind Myhre, Flore Sicre de Fontbrune, Ulla Wartiovaara-Kautto, Vincent T. Ho, Jolanta Gozdzik, Austin G Kulasekararaj, Syed Rafat Ali Jafri, Antonio M. Risitano, Abdulrahman Alsultan, R. Grant Rowe, Namik Yasar Ozbek, Samppa Johannes Ryhänen, Corey S. Cutler, Urpu Salmenniemi, Kirsi Jahnukainen
article en

Abstract

The hallmark of ERCC6L2 disease (ED) is a highly penetrant progression from bone marrow failure (BMF) to erythroid-predominant, TP53-mutated myeloid malignancy with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option, but concerns exist regarding transplant-related toxicities due to the underlying DNA repair defect. 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), transplant-related toxicity, and non-relapse mortality (NRM). The 1-year and 3-year OS were 79% (95% confidence interval [CI], 66-91) and 54% (95% CI, 35-73), respectively. Prior history of excess blasts significantly predicted inferior survival (hazard ratio [HR], 6.8; 95% CI, 2.2-20.3; P<0.001), with a median survival of 12 months (95% CI, 0-24). Grade 3-5 endothelial toxicities occurred in 27% of patients and were associated with higher NRM (HR, 7.7; 95% CI, 1.5-38.8; P=0.016). The use of non-treosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared to reduced-intensity conditioning (RIC) (HR, 4.9; 95% CI, 1.1-22.0; P=0.040), 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 i.e. 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.

Blood Advances
Jagiellonian University (PL), Oslo University Hospital (NO), Boston Children's Hospital (US), Karolinska University Hospital (SE), University of Helsinki (FI), University College London Hospitals NHS Foundation Trust (GB), University Hospital Centre Zagreb (HR), Ankara University (TR), University of Health Science (KH), Universidade de Santiago de Compostela (ES), Université Paris Cité (FR), Oulu University Hospital (FI), King Hussein Cancer Center (JO), Southampton Hospital (US), Helsinki University Hospital (FI), King Faisal Specialist Hospital & Research Centre (SA), Southampton General Hospital (GB), King Saud University (SA), Karolinska Institutet (SE), Uniwersytecki Szpital Dziecięcy (PL), Integrated Oncology (United States) (US), Complejo Hospitalario Universitario de Santiago (ES), Assistance Publique – Hôpitaux de Paris (FR), Memorial Ankara Hospital (TR), European Society for Blood and Marrow Transplantation (NL), Dana-Farber Cancer Institute (US), Hôpital Robert-Debré (FR), Sağlık Bilimleri Üniversitesi (TR), Hôpital Saint-Louis (FR), Cancer Society of Finland (FI), Krakow Cardiovascular Research Institute (PL), Boston Children's Museum (US), Banc de Sang i Teixits (ES), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), Technical University of Munich (DE), Newcastle University (GB)
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, Instituto de Salud Carlos III, European Regional Development Fund
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Openalex Percentile: Top 72%
Acute Myeloid Leukemia Research
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