Allogeneic hematopoietic stem cell transplantation in patients with germ line DDX41 mutated myeloid malignancies
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood Advances
Authors: Michael Loschi, Marie-Charlotte Villy, Jacques-Emmanuel Galimard, Marie-Mathilde Auboiroux, Nathalie Gachard, Alexandre Perani, Matthieu Duchmann, Laetitia Largeaud, Stéphanie Nguyen, Flore Sicre de Fontbrune, Marie Robin, Ibrahim Yakoub-Agha, Etienne Daguindau, Sylvain Chantepie, Amandine Charbonnier, Delphine Lebon, Sébastien Maury, Hélène Labussiere-Wallet, Anne Huynh, Edouard Forcade, Cristina Castilla-Llorente, Thomas Cluzeau, Lionel Adès, Maud D’aveni, Raynier Devillier, Natacha Maillard, Sami Benachour, Hervé Dombret, Christian Récher, Arnaud Pigneux, Emmanuelle Clappier, Eric Delabesse, Nicolas Duployez, Pascal Turlure, Régis Peffault de Latour, Marie Sébert
Institutions: Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Hôpital Saint-Louis, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, European Society for Blood and Marrow Transplantation, Centre Hospitalier Universitaire de Limoges, Université de Limoges, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Pitié-Salpêtrière Hospital, Université de Lille, Centre Hospitalier Universitaire de Lille, Institute for Translational Research in Inflammation, Centre Hospitalier Universitaire de Besançon, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Universitaire Amiens-Picardie, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, Hospices Civils de Lyon, Hôpital Lyon Sud, Centre Hospitalier Universitaire de Bordeaux, Institut Gustave Roussy, Fondation Gustave Roussy, Université Paris Cité, Génomes, biologie cellulaire et thérapeutiques, Centre Hospitalier Régional et Universitaire de Nancy, Université de Lorraine, Institut Paoli-Calmettes, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Hôpital Cardiologique du Haut-Lévêque, Centre de Recherches en Cancérologie de Toulouse, Université de Toulouse
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4414084038