Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome

Hsin-An Hou, Cheng-Hong Tsai, Chien-Chin Lin, Wen-Chien Chou, Yuan-Yeh Kuo, Chieh-Yu Liu, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Xiu-Wen Liao, Liang-In Lin, Ming Yao, Jih-Luh Tang, Hwei-Fang Tien, Hsin-An Hou, Cheng-Hong Tsai, Chien-Chin Lin, Wen-Chien Chou, Yuan-Yeh Kuo, Chieh-Yu Liu, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Xiu-Wen Liao, Liang-In Lin, Ming Yao, Jih-Luh Tang, Hwei-Fang Tien

Abstract

Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1, DNMT3A, and TP53 were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (P < 0.001 for both OS and leukemia-free survival). In conclusion, integration of gene mutations in current IPSS-R improves the prognostication of MDS patients and may help identify high-risk patients for more aggressive treatment in IPSS-R lower risk group.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Pairwise associations among gene mutations in 426 MDS patients
Fig. 2. Overall survival and leukemia transformation…
Fig. 2. Overall survival and leukemia transformation rate according to the revised International Prognostic Scoring System (IPSS-R) risk categories and mutational status.
a–d Overall survival according to the presence or absence of poor-risk mutations (CBL, IDH2, ASXL1, DNMT3A, and TP53 mutations) and IPSS-R. e–h Leukemia transformation rate according to the presence or absence of poor-risk mutations (CBL, IDH2, ASXL1, DNMT3A, and TP53 mutations) and IPSS-R
Fig. 3. Overall survival and leukemia transformation…
Fig. 3. Overall survival and leukemia transformation rate according to 2016 WHO classification risk categories and mutational status.
a, c, e Overall survival according to the presence or absence of poor-risk mutations (CBL, IDH2, ASXL1, DNMT3A, and TP53 mutations) and 2016 WHO classification. b, d, f Leukemia transformation rate according to the presence or absence of poor-risk mutations (CBL, IDH2, ASXL1, DNMT3A, and TP53 mutations) and 2016 WHO classification
Fig. 4
Fig. 4
Kaplan–Meier estimates of overall survival (a) and leukemia transformation rate (b) based on integrated IPSS-R and mutational analyses in the 426 FAB-defined MDS patients
Fig. 5
Fig. 5
Kaplan–Meier estimates of overall survival (a) and leukemia transformation rate (b) based on integrated IPSS-R and mutational analyses in the 328 WHO-defined MDS patients

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