The most frequent genetic susceptibility to myelodysplastic syndrome and acute myeloid leukemia (AML) is DDX41 germline mutations (DDX41MutGL). DDX41MutGL myeloid cancers may be regarded as a separate entity, according to recent findings, even when their exact presentation and prognosis were unknown. For a study, researchers sought to outline the molecular and clinical characteristics of 191 individuals with DDX41MutGL AML.

These individuals’ baseline characteristics and outcomes were compared to those of 1,604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%, in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization studies. Most DDX41MutGL AML patients were male (75%), in their seventh decade, with normal cytogenetics (75%), few other somatic mutations, low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), and low bone marrow blast infiltration (median, 2).

Eighty-two percent of patients had a second somatic DDX41 mutation, known as DDX41MutSom, and clonal architecture inference showed that it could be the primary factor for AML to proceed. In comparison to 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P<.001), DDX41MutGL patients had higher complete remission rates (94% vs 69%; P<.0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT). Relapse rates censored at HSCT were lower in patients with DDX41MutGL at 1 year (15% vs 44%) but eventually rose to be comparable to individuals with Int/Adv DDX41WT at 3 years (82% vs 75%).

HSCT in the first complete remission was linked to a longer relapse-free survival (hazard ratio, 0.43; 95% CI: 0.21-0.88; P=.02), but not a longer overall survival (hazard ratio, 0.77; 95%CI: 0.35-1.68; P=.5).