Outcomes of allogeneic transplant in patients with DDX41 mutated myelodysplastic syndrome and acute myeloid leukemia

Characteristics and clinical outcomes of patients with myeloid malignancies and DDX41 variants

“…HSCT outcomes in patients with DDX41 is a key recent issue due to the high reported incidence of severe GVHD, with one study reporting grade 3-4 acute GVHD in 38% of transplanted patients with DDX41 mutations. 20,21 Our study did not specifically assess the rates and severity of GVHD. However, the outcomes reported after HSCT in our cohort appear favorable.…”

“…A recent study by Duployez et al analyzed the outcomes of a large cohort of intensively‐treated patients with DDX41 germline mutations and suggested a better outcome in DDX41 ‐mutated cases compared to wild‐type cases 19 . Moreover, there is a unique concern regarding patients with DDX41 mutations that undergo hematopoietic stem cell transplantation (HSCT), as recent publications suggest these patients may have an impaired survival due to an increased risk of severe acute graft versus host disease (GVHD) 20,21 . In this study, we analyzed one of the largest cohorts of patients with DDX41 variants, with special emphasis on response to therapy and clinical outcomes as well as the impact of HSCT.…”

Venetoclax plus hypomethylating agents in DDX41‐mutated acute myeloid leukaemia and myelodysplastic syndrome: Mayo Clinic series on 12 patients

“…The mOS for MDS/AML series and AML patients was 29 months (Figure 1B). All AML patients received HMA + VEN (two patients received VEN/decitabine combination while all other AML patients received VEN/azacitidine) achieved remissions, with median number of cycles to achieve marrow response was 2 (1-3), and the median total number of cycles of HMA + VEN was 8 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). All patients had haematological response (HR) at the time of morphological remission (MR) and eight (88%) had HR preceding the morphological response (one patient did not have CBC until one obtained at bone marrow biopsy to assess response) (Table S1).…”

“…[7][8][9][10] Interestingly mDDX41 MNs have higher non-relapse-related mortality in patients receiving allogeneic haematopoietic cell transplantation (HCT). [10][11][12][13] Nonetheless, the current knowledge of mDDX41 MN is largely limited, and the best therapeutic option is unknown. The molecular profile of mDDX41 was associated with increased responsiveness to lenalidomide and recently Makishima et al, reported better OS in mDDX41 AML than DDX41-WT AML and HR-MDS regardless of treatment option with better prognosis in patients receiving HMA treatment.…”

Observation and treatment in DDX41-mutated acute myeloid leukemia and myelodysplastic syndrome

“…It has been recently linked to more a favorable outcome despite its presentation with higher grade MDS and AML with higher response rates and long overall survival [ 4 , 5 ]. Additionally, allogeneic hematopoietic cell transplantation (HCT), the only potentially curative option, has been linked to higher non-relapse mortality and therefore potentially to consider delayed HCT at disease progression or relapse [ 4 , 6 ]. Some DDX41 mutations can potentially be of germline origin and such work-up is warranted in these cases [ 7 ].…”