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An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome
Sang Kyun Sohn1, Joon Ho Moon1, In Hee Lee1
1Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea.
Background/Aims:
This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System.
Methods:
A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed.
Results:
HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS.
Conclusion:
For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.
Insights
Hypomethylating agents (HMA) did not improve overall survival for high-risk myelodysplastic syndrome (MDS) patients compared to best supportive care (BSC). Allogeneic hematopoietic cell transplantation (allo-HCT) was the only factor predicting favorable long-term outcomes in MDS.
Area of Science:
- Hematology
- Oncology
- Clinical Research
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- High or very-high (H/VH) risk MDS patients have a poor prognosis.
- Evaluating treatment efficacy in H/VH risk MDS is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the role of hypomethylating agents (HMA) versus best supportive care (BSC) in H/VH risk MDS patients.
- To identify prognostic factors influencing overall survival (OS) in this patient population.
- To assess the impact of HMA on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes.
Main Methods:
- Retrospective analysis of 279 H/VH risk MDS patients from the Korean MDS Working Party database.
- Comparison of OS rates between patients receiving HMA, BSC, or allo-HCT (with or without HMA).
- Multivariate analysis to identify factors associated with OS.
Main Results:
- HMA therapy was administered to 73.5% of patients; 11.1% received allo-HCT post-HMA.
- Three-year OS rates: allo-HCT with HMA (53.1%), allo-HCT without HMA (75%), HMA alone (17.3%), BSC (20.8%).
- Multivariate analysis identified allo-HCT as the only favorable prognostic factor; poor cytogenetics, age ≥ 65, ECOG PS 2-4, and AML transformation were adverse factors.
Conclusions:
- HMA did not demonstrate a survival benefit over BSC for H/VH risk MDS.
- Allogeneic hematopoietic cell transplantation (allo-HCT) is the sole predictor of favorable long-term survival.
- HMA use did not negatively impact allo-HCT outcomes, but further large-scale research is warranted.
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