scholarly journals Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

2019 ◽  
Vol 111 (2) ◽  
pp. 580-591 ◽  
Author(s):  
Lingxu Jiang ◽  
Yingwan Luo ◽  
Shuanghong Zhu ◽  
Lu Wang ◽  
Liya Ma ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Mutation Status ◽  
Prognostic Prediction

scholarly journals Mutation Status and Burden Can Improve Prognostic Prediction of Patients with Lower-Risk Myelodysplastic Syndromes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3008-3008
Author(s):  
Lingxu Jiang ◽  
Yingwan Luo ◽  
Jie Jin ◽  
Hongyan Tong
Keyword(s):  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Prognostic Models ◽  
Molecular Profile ◽  
International Prognostic Scoring System ◽  
Mutation Status ◽  
Prognostic Prediction

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using next-generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P=0.001), RUNX1 (P=0.031), EZH2 (P=0.049), TP53 (P=0.016), SRSF2 (P=0.046), JAK2 (P=0.040), and IDH2 (P=0.035). We also found significantly shorter OS in patients with a TET2 variant allele frequency (VAF) ≥18% versus those with either a TET2 VAF <18% or without TET2 mutations (median: 20.4 vs. 47.8 months; P=0.020; HR=2.183, 95%CI: 1.129-4.224). After adjustment for the IPSS, shorter OS was associated with mutation status of ASXL1 (P<0.001; HR=4.306, 95%CI: 2.144-8.650), TP53 (P=0.004; HR=4.863, 95%CI: 1.662-14.230) and JAK2 (P=0.002; HR=5.466, 95%CI: 1.848-16.169), as well as a TET2 VAF ≥18% (P=0.008; HR=2.492, 95%CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P<0.001). A novel prognostic scoring system based on the IPSS and the presence/absence of the 4 independent mutational factors further stratified LR-MDS patients into three prognostically different groups (P<0.001).The newly developed scoring system re-defined 10.1% (16/159) of patients as higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDSand could help identify those with worse-than-expected prognosis for more aggressive treatment. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Content validity of patient-reported outcomes for use in lower-risk myelodysplastic syndromes

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Jeremiah J. Trudeau ◽  
Jianming He ◽  
Esther Rose ◽  
Charlotte Panter ◽  
Sharan Randhawa ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Content Validity ◽  
Lower Risk ◽  
Patient Reported Outcomes ◽  
Patient Reported

scholarly journals TET2 Mutation and High miR-22 Expression as Biomarkers to Predict Clinical Outcome in Myelodysplastic Syndrome Patients Treated with Hypomethylating Therapy

2021 ◽  
Vol 43 (2) ◽  
pp. 917-931
Author(s):  
Jina Yun ◽  
Young Sok Ji ◽  
Geum Ha Jang ◽  
Sung Hee Lim ◽  
Se Hyung Kim ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Odds Ratio ◽  
Lower Risk ◽  
Genetic Mutations ◽  
Dna Hypermethylation ◽  
Leukemic Transformation ◽  
Mutation Status ◽  
Similar Tendency ◽  
Tet2 Mutation ◽  
Expression Status

Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = −0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.

scholarly journals Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents

2011 ◽  
Vol 156 (5) ◽  
pp. 619-625 ◽  
Author(s):  
David Sibon ◽  
Giovanna Cannas ◽  
Fiorenza Baracco ◽  
Thomas Prebet ◽  
Norbert Vey ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Erythropoiesis Stimulating Agents

Rationale for Therapy Discontinuation in Patients with Lower-Risk Transfusion-Dependent Myelodysplastic Syndromes (LR-MDS)

2017 ◽  
Vol 55 ◽  
pp. S140-S141
Author(s):  
A.T. Gerds ◽  
S. Gupta ◽  
M.A. Sekeres ◽  
A. Nazha ◽  
H.E. Carraway ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Therapy Discontinuation

Validation of the Lower Risk MD Anderson Prognostic Scoring System for Patients with Myelodysplastic Syndromes (MDS)

2015 ◽  
Vol 15 ◽  
pp. S232-S233
Author(s):  
Hanadi Ramadan ◽  
Maria Corrales-Yepez ◽  
Najla Ali ◽  
Ling Zhang ◽  
Eric Padron ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Md Anderson

Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study

2006 ◽  
Vol 24 (16) ◽  
pp. 2465-2471 ◽  
Author(s):  
Norbert Vey ◽  
Andre Bosly ◽  
Agnes Guerci ◽  
Walter Feremans ◽  
Herve Dombret ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
International Prognostic Scoring System ◽  
Risk Category ◽  
Moderate Activity ◽  
Loading Dose ◽  
Median Response ◽  
System Risk

Purpose Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS). Patients and Methods MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation. Results Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients. Conclusion Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.

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