PROGNOSTIC MUTATIONS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME TREATED WITH HEMATOPOIETIC STEM-CELL TRANSPLANTATION
Author(s): ,
Zixian Liu
Affiliations:
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin,China
,
Shanbo Cao
Affiliations:
AcornMed Biotechnology Co. Ltd,Beijing,China
,
Feng Lou
Affiliations:
AcornMed Biotechnology Co. Ltd,Beijing,China
,
Ying Sun
Affiliations:
AcornMed Biotechnology Co. Ltd,Beijing,China
,
Erlie Jiang
Affiliations:
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin,China
Mingzhe Han
Affiliations:
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin,China
EHA Library. Liu Z. Jun 14, 2019; 266348; PF548
Dr. Zixian Liu
Dr. Zixian Liu
Contributions
Abstract

Abstract: PF548

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Genetic mutations in MDS patients are closely related with clinical phenotypes and prognosis in MDS patients. But whether mutations are prognostic for outcomes after allogeneic hematopoietic stem-cell transplantation(allo-HSCT) remains to be elaborated.

Aims
This research was done to figure out whether genetic mutations help the risk-stratification in MDS patients received transplantation.

Methods
Targeted mutational analysis were performed on samples obtained before transplantation from 151 patients underwent HSCT. Overall-survival(OS) was calculated from the date of transplantation to date of death, and surviving patients were censored at the date on which they were last known to be alive. Diease-free survival(DFS) was calculated from the time of transplantation to date of relapse or death and was censored at the last date known to alive without relapse. We analyzed the relationship of mutations and clinical outcomes. Curves for OS and DFS were generated using the Kaplan-Meier method and compared using log-rank test.Cumulative incidence of nonrelapse death and relapse was assessed using competing risks from time of HSCT to nonrelapse death or relapse by the Gray test.

Results
All 151 patients carried more than one mutations, most frequently in DNAH2(47.02%), KDM6B(42.38%), USH2A(41.06%), KMT2D(38.41%), PCLO(33.11%), CCDC168(32.45%), U2AF1(29.14%), TET2(27.81%), ASXL1(25.83%), ARID1B(23.18%). In univariable analyses, TP53 or PPM1D mutations, ANKRD26 mutations, FLT3 abnormalities(including FLT3-ITD), PDGFRB mutations were associated with shorter OS(TP53 or PPM1D, P=0.064; ANKRD26, P=0.025, FLT3 abnormalities: P=0.046; PDGFRB, P=0.044) and DFS(TP53 or PPM1D, P=0.019; ANKRD26, P=0.058, FLT3 abnormalities: P=0.047; PDGFRB, P=0.048). In multivariable analysis including clinical variables, monosomal karyotype status, HCT-CI, and candidate genes, PDGFRB mutations and FLT3 abnormalities were each independently associated with shorter OS(PDGFRB mutations, HR=2.979, P=0.021; FLT3 abnormalities, HR=2.677, P=0.018) and DFS(PDGFRB mutations, HR=2.779, P=0.019; FLT3 abnormalities, HR=2.288, P=0.03). PDGFRB mutations(P=0.042), ANKRD26 mutations (P=0.004) were associated with higher non-relapse mortality rate. FLT3 abnormalities was associated with higher relapse rate in RAEB patients(P=0.004).

Conclusion
 PDGFR mutations and FLT3 abnormalities are independently associated with  shorter survival in MDS patients treated with allo-HSCT.

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Allo-SCT, MDS, Mutation

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