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. 2025 Dec 23;9(24):6314-6325.
doi: 10.1182/bloodadvances.2025017084.

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

Michael Loschi  1 , Marie-Charlotte Villy  2 , Jacques-Emmanuel Galimard  3 , Marie-Mathilde Auboiroux  4 , Nathalie Gachard  5 , Alexandre Perani  6 , Matthieu Duchmann  7 , Laetitia Largeaud  8 , Stéphanie Nguyen  9 , Flore Sicre de Fontbrune  10 , Marie Robin  10 , Ibrahim Yakoub-Agha  11 , Etienne Daguindau  12 , Sylvain Chantepie  13 , Amandine Charbonnier  14 , Delphine Lebon  14 , Sébastien Maury  15 , Hélène Labussiere-Wallet  16 , Anne Huynh  17 , Edouard Forcade  18 , Cristina Castilla-Llorente  19 , Thomas Cluzeau  1 , Lionel Adès  20 , Maud D'aveni  21 , Raynier Devillier  22 , Natacha Maillard  23 , Sami Benachour  1 , Hervé Dombret  20 , Christian Récher  17 , Arnaud Pigneux  18 , Emmanuelle Clappier  7 , Eric Delabesse  17 , Nicolas Duployez  11 , Pascal Turlure  4 , Régis Peffault de Latour  10 , Marie Sébert  20
Affiliations

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

Michael Loschi et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flowchart summarizing patients included in each analysis.
Figure 2.
Figure 2.
Outcomes of the 83 patients with DDX41mut. (A) OS. (B) LFS. (C) Cumulative incidence of relapse. (D) Cumulative incidence of NRM. (E) Cumulative incidence of grade 2 to 4 aGVHD. (F) Cumulative incidence of cGVHD.
Figure 3.
Figure 3.
Outcomes of the 109 pair-matched patients with AML (77 DDX41WT and 32 DDX41mut). (A) LFS. (B) OS. (C) Cumulative incidence of relapse. (D) Cumulative incidence of NRM. (E) Cumulative incidence of grade 2 to 4 acute GVHD. (F) Cumulative incidence of cGVHD.
Figure 4.
Figure 4.
DCL. Features and outcomes of the 7 patients who experienced DCL after a first related HSCT.
See this image and copyright information in PMC

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