Fiche publication
Date publication
septembre 2025
Journal
Blood advances
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAGUINDAU Etienne
,
Dr D'AVENI-PINEY Maud
Tous les auteurs :
Loschi M, Villy MC, Galimard JE, Auboiroux MM, Gachard N, Perani A, Duchmann M, Largeaud L, Nguyen S, Sicre de Fontbrune F, Robin M, Yakoub-Agha I, Daguindau E, Chantepie SP, Charbonnier A, Lebon D, Maury S, Labussiere-Wallet H, Huynh A, Forcade E, Castilla-Llorente C, Cluzeau T, Adès L, D'Aveni M, Devillier R, Maillard N, Benachour S, Dombret H, Récher C, Pigneux A, Clappier E, Delabesse E, Duployez N, Turlure P, Peffault De Latour R, Sebert M
Lien Pubmed
Résumé
Germline DDX41 mutations (DDX41mut) are identified in approximately 5% of myeloid malignancies with excess of blasts, representing a distinct MDS/AML entity. The disease is associated with better outcomes compared to DDX41 wild-type (DDX41WT), but patients who do not undergo allogeneic hematopoietic stem cell transplantation (HSCT) may experience late relapse. Due to the recent identification of DDX41mut, data on post-HSCT outcomes remain limited. Here, we first report the HSCT outcomes of 83 DDX41mut MDS/AML patients. With a median follow-up (FU) of 4.4 years, the 2-year leukemia-free survival (LFS) was 68.6% (95% CI, 57.1 - 77.6), with a 2-year non-relapse mortality (NRM) of 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 transplantation in AML clinical trials. No significant differences were observed between DDX41mut and DDX41WT patients in terms of LFS at 2 years (HR: 1.06, 95% CI, 0.59-1.90, p=0.84), overall survival (OS), NRM, relapse, or graft-versus-host disease (GVHD) incidence. The CIR for DDX41mut showed a trend toward a lower relapse rate during the first year and a higher relapse rate after 1 year. Given the familial nature of the disease, we specifically examined patients who relapsed after HSCT with a related donor, identifying 7 cases of DDX41mut donor cell leukemia (DCL). In our study, HSCT in DDX41mut AML patients was not associated with an increased risk of toxicity. However, we observed a potential for later relapse, which could potentially be mitigated by selecting related donors based on DDX41 status.
Référence
Blood Adv. 2025 09 9;:
