Allogeneic hematopoietic stem cell transplantation in patients with germ line <i>DDX41</i> mutated myeloid malignancies

Germ line DDX41 mutations (DDX41mut) are identified in ∼5% of myeloid malignancies with an excess of blasts, representing a distinct myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) entity. The disease is associated with better outcomes than DDX41 wild-type (DDX41WT) cases, but patients who do not undergo allogeneic hematopoietic stem cell transplantation (HSCT) may experience late relapse. Because of the recent identification of DDX41mut, data on the post-HSCT outcomes remain limited. In this study, we report the HSCT outcomes of 83 patients with DDX41mut MDS/AML. With a median follow-up of 4.4 years, the 2-year leukemia-free survival (LFS) was 68.6% (95% confidence interval [CI], 57.1-77.6) and the 2-year nonrelapse mortality (NRM) was 21.1% (95% CI, 12.9-30.6). We then assessed the impact of DDX41mut using a pair match analysis performed on patients who underwent a transplantation in AML clinical trials. No significant differences were observed between patients with DDX41mut and those with DDX41WT in terms of LFS at 2 years (hazard ratio, 1.06; 95% CI, 0.59-1.90; P = .84), overall survival, NRM, relapse, or graft-versus-host disease incidence. The cumulative incidence of relapse for DDX41mut showed a trend toward a lower relapse rate during the first year then higher after 1 year. Given the familial nature of the disease, we specifically examined patients who relapsed after HSCT with a related donor and identified 7 cases of DDX41mut donor cell leukemia. In this study, HSCT in patients with DDX41mut AML was not associated with an increased risk for toxicity. However, we observed a potential for later relapse, which could potentially be mitigated by selecting related donors based on DDX41 status.

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Publication Details

Journal
Blood Advances
Published
2025-09-09
DOI
https://doi.org/10.1182/bloodadvances.2025017084
Citations
2
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
3.54
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article

Allogeneic hematopoietic stem cell transplantation in patients with germ line DDX41 mutated myeloid malignancies

Hervé Dombret, Arnaud Pigneux, Laëtitia Largeaud, Lionel Adès et al.
2 citations
Blood Advances
Acute Myeloid Leukemia Research
3.54
article

Allogeneic hematopoietic stem cell transplantation in patients with germ line DDX41 mutated myeloid malignancies

Hervé Dombret, Arnaud Pigneux, Laëtitia Largeaud, Lionel Adès, Éric Delabesse, Marie Robin, Christian Récher, Sébastien Maury, Michael L. Loschi, Sylvain Chantepie, Emmanuelle Clappier, Pascal Turlure, Alexandre Perani, Anne Huynh, Matthieu Duchmann, Étienne Daguindau, Cristina Castilla‐Llorente, Delphine Lebon, Marie Sébert, Ibrahim Yakoub‐Agha, Marie‐Charlotte Villy, Raynier Devillier, Sami Benachour, Jacques‐Emmanuel Galimard, A Charbonnier, Flore Sicre de Fontbrune, Thomas Cluzeau, Régis Peffault de Latour, Nathalie Gachard, Maud D’Aveni, Nicolas Duployez, Hélène Labussière‐Wallet, Marie-Mathilde Auboiroux, Édouard Forcade, Stéphanie Nguyen, Natacha Maillard
article en
2 citations

Abstract

Germ line DDX41 mutations (DDX41mut) are identified in ∼5% of myeloid malignancies with an excess of blasts, representing a distinct myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) entity. The disease is associated with better outcomes than DDX41 wild-type (DDX41WT) cases, but patients who do not undergo allogeneic hematopoietic stem cell transplantation (HSCT) may experience late relapse. Because of the recent identification of DDX41mut, data on the post-HSCT outcomes remain limited. In this study, we report the HSCT outcomes of 83 patients with DDX41mut MDS/AML. With a median follow-up of 4.4 years, the 2-year leukemia-free survival (LFS) was 68.6% (95% confidence interval [CI], 57.1-77.6) and the 2-year nonrelapse mortality (NRM) was 21.1% (95% CI, 12.9-30.6). We then assessed the impact of DDX41mut using a pair match analysis performed on patients who underwent a transplantation in AML clinical trials. No significant differences were observed between patients with DDX41mut and those with DDX41WT in terms of LFS at 2 years (hazard ratio, 1.06; 95% CI, 0.59-1.90; P = .84), overall survival, NRM, relapse, or graft-versus-host disease incidence. The cumulative incidence of relapse for DDX41mut showed a trend toward a lower relapse rate during the first year then higher after 1 year. Given the familial nature of the disease, we specifically examined patients who relapsed after HSCT with a related donor and identified 7 cases of DDX41mut donor cell leukemia. In this study, HSCT in patients with DDX41mut AML was not associated with an increased risk for toxicity. However, we observed a potential for later relapse, which could potentially be mitigated by selecting related donors based on DDX41 status.

Blood AdvancesVol. 9(24)
Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Lyon College (US), Université Côte d'Azur (FR), Université Paris Cité (FR), Institut National Polytechnique de Toulouse (FR), Université de Lille (FR), Institut Gustave Roussy (FR), Saint Louis University Hospital (US), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Toulouse (FR), Université de Poitiers (FR), Sorbonne Université (FR), Centre de Recherches en Cancérologie de Toulouse (FR), Centre Hospitalier Universitaire de Besançon (FR), Acute Leukemia French Association (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Toulouse Mathematics Institute (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Délégation Centre-Est (FR), Centre Hospitalier Universitaire de Poitiers (FR), Hôpital Lyon Sud (FR), Centre Hospitalier Universitaire de Limoges (FR), Hôpital Cardiologique du Haut-Lévêque (FR), Pitié-Salpêtrière Hospital (FR), Hôpitaux Universitaires Henri-Mondor (FR), Hôpital Saint-Louis (FR), Institut Paoli-Calmettes (FR), European Society for Blood and Marrow Transplantation (FR), Université de Limoges (FR), Université de Lorraine (FR), Université de Caen Normandie (FR)
Openalex Percentile: Top 6%
Acute Myeloid Leukemia Research
3.54
DOIOpen Access PDFOpenAlex
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