Contributions
Abstract: EP929
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background
The World Health Organization has included myeloid neoplasms with germline predisposition into its classification since 2016. Especially, DDX41 mutation is clinically unique due to its late onset compared with other germline lesions, such as CEBPA and GATA2.
Aims
This study was aimed to report the clinical features of DDX41-mutated myeloid neoplasms and describe phenotypes of different diagnosed entities utilizing both study- and individual- level data.
Methods
“DDX41” was searched in PubMed and Web of science between 2015/01/01 and 2020/12/31, with additional manual searching and individual-patient data seeking. Both study- and individual- level data were utilized to present the clinical features of the whole population and patients in different subgroups.
Results
7 articles with 177 patients were finally included. Patients harboring mutated DDX41 contributed to 3.1% [95%CI 2.7-3.6%] of myeloid neoplasms, with 81.3% [95%CI 69.6-90.7%] males and mean diagnosed age of 65.6 years [95%CI 62.9-68.3]. DDX41-mutattions were most common in patients with myelodysplastic syndromes (MDS) with excess blast-1/2 (38.7%) and acute myelocytic leukemia (AML, 36.8%). 76.9% [95%CI 59.9-90.2%] of patients carrying DDX41-mutattions had normal karyotype. 75.1% [95%CI 53.1-91.7%] patients had germline and 76.3% [95%CI 59.6-89.6%] patients had somatic DDX41 variants. ASXL1 and TP53 were the top frequent concomitant somatic mutations. The pooled overall response rate for hypomethylating agents was 71.0% [95%CI 54.1-85.4] and all the patients with AML achieved complete remission at the first course. The median overall survival was between 32 months to not reached. Familial cases had younger age (p=0.0001), more germline p.D140fs variant (OR=2.88 [95%CI 1.09-7.76], p=0.021) and better response to treatment compared with sporadic cases.
Conclusion
Myeloid neoplasms carrying DDX41-mutations were mainly older, male, MDS EB-1/2 and AML patients. They had better response to the treatment and possible longer survival. Familial cases were diagnosed earlier and had more favorable response to treatment than sporadic cases.
Keyword(s): Mutation, Myeloid malignancies
Abstract: EP929
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background
The World Health Organization has included myeloid neoplasms with germline predisposition into its classification since 2016. Especially, DDX41 mutation is clinically unique due to its late onset compared with other germline lesions, such as CEBPA and GATA2.
Aims
This study was aimed to report the clinical features of DDX41-mutated myeloid neoplasms and describe phenotypes of different diagnosed entities utilizing both study- and individual- level data.
Methods
“DDX41” was searched in PubMed and Web of science between 2015/01/01 and 2020/12/31, with additional manual searching and individual-patient data seeking. Both study- and individual- level data were utilized to present the clinical features of the whole population and patients in different subgroups.
Results
7 articles with 177 patients were finally included. Patients harboring mutated DDX41 contributed to 3.1% [95%CI 2.7-3.6%] of myeloid neoplasms, with 81.3% [95%CI 69.6-90.7%] males and mean diagnosed age of 65.6 years [95%CI 62.9-68.3]. DDX41-mutattions were most common in patients with myelodysplastic syndromes (MDS) with excess blast-1/2 (38.7%) and acute myelocytic leukemia (AML, 36.8%). 76.9% [95%CI 59.9-90.2%] of patients carrying DDX41-mutattions had normal karyotype. 75.1% [95%CI 53.1-91.7%] patients had germline and 76.3% [95%CI 59.6-89.6%] patients had somatic DDX41 variants. ASXL1 and TP53 were the top frequent concomitant somatic mutations. The pooled overall response rate for hypomethylating agents was 71.0% [95%CI 54.1-85.4] and all the patients with AML achieved complete remission at the first course. The median overall survival was between 32 months to not reached. Familial cases had younger age (p=0.0001), more germline p.D140fs variant (OR=2.88 [95%CI 1.09-7.76], p=0.021) and better response to treatment compared with sporadic cases.
Conclusion
Myeloid neoplasms carrying DDX41-mutations were mainly older, male, MDS EB-1/2 and AML patients. They had better response to the treatment and possible longer survival. Familial cases were diagnosed earlier and had more favorable response to treatment than sporadic cases.
Keyword(s): Mutation, Myeloid malignancies