Aim:

Germline DDX41 mutations define specific myeloid neoplasm subtypes including AML and MDS. Whilst DDX41-mutated patients often undergo allogeneic haematopoietic stem cell transplant (HSCT), recent retrospective analyses have reported higher severe acute and chronic graft vs host disease (GVHD)1 and inferior survival2 compared to non-DDX41 mutated patients. We aimed to review the outcomes of patients transplanted at our center for myeloid neoplasms with germline DDX41 (MN-DDX41).

Method:

We conducted a retrospective analysis of all patients treated at our institution for MN-DDX41 between January 2019 to January 2024. Data collected included disease characteristics, genomic data, treatment details, response outcomes and survival. The primary endpoint was overall survival (OS), with secondary endpoints including treatment-related mortality (TRM), relapse, and GVHD incidence.

Results:

22 patients with MN-DDX41 were identified (8 AML, 14 MDS). Median age at diagnosis was 64 (range 59-75 years), with 18 (87%) male. Donor source was matched sibling (1; 7%), matched unrelated (11; 79%) or mismatched unrelated (2; 14%); conditioning was reduced-intensity or non-myeloablative in 13 and 1 respectively; GVHD prophylaxis was CsA/MTX in 8 (57%) and PTCy/tacrolimus/MMF in 6 (43%). After median follow-up of 27 months (range 6-64mo), 17 (77%) are alive; 4 patients not receiving HSCT died from progressive/refractory disease, and 1 HSCT recipient died from infection soon after engraftment. For HSCT recipients, after median follow-up 18 months post-HSCT (range 1-45mo), 13 (93%) remain alive in remission. The cumulative incidences of acute (grade II-IV) and moderate-severe chronic GVHD are 35% and 50% respectively. OS following original diagnosis showed a non-significant trend for HSCT recipients vs non-recipients (2-yr OS 90% vs 65%; p=0.19).

Conclusion:

Despite adverse risk factors our early single-centre experience suggests that allogeneic HSCT is acceptably safe and efficacious for patients with MN-DDX41, and supports its use compared to non-HSCT alternatives. Confirmation in larger, multicentre studies with longer follow-up is warranted.

References:

  1. Saygin C, Roloff G, Hahn CN, Chhetri R, Gill S, Elmariah H, et al. Allogeneic hematopoietic stem cell transplant outcomes in adults with inherited myeloid malignancies. Blood Adv. 2023 Feb 17;7(4):549-54.

  2. Baranwal A, Nanaa A, Viswanatha D, He R, Foran J, Badar T, et al. Outcomes of allogeneic transplant in patients with DDX41 mutated myelodysplastic syndrome and acute myeloid leukemia. Bone Marrow Transplant. 2022 Nov;57(11):1716-8.

Disclosures

Henden:Astra Zeneca: Honoraria; Astellas: Honoraria; Gilead: Honoraria.

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2024
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