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Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis.

Jin J, Hu C, Yu M, Chen F, Ye L, Yin X, Zhuang Z, Tong H - PLoS ONE (2014)

Bottom Line: In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023).The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS.Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

ABSTRACT

Background: Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).

Methods: Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.

Results: In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.

Conclusion: The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.

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pone-0100206-g001: Flow diagram of study selection.

Mentions: To further assess the relationship between IDH1/2 mutations and MDS risk, we conducted a meta-analysis combining our study data with published studies on IDH mutations in MDS [3], [14], [15], [16], [17], [18]. Two independent reviewers (CH and MXY) performed a systematic literature search using ISI Web of Science, PubMed and the Cochrane Library for relevant papers published before December 2013 by the search term “(MDS OR myelodysplastic syndrome OR preleukemia OR myelodysplasia) AND (IDH1 OR IDH2).” Reviews and references of related articles were checked for missing information. Eligible papers met all the following criteria: (1) assessed the association between IDH1/2 mutations and outcomes in MDS; (2) detailed survival information of patients with IDH1 or IDH2 mutations; (3) reported the study in English. Animal studies, letters to the editor without original data, reviews and case reports were excluded. In the event of multiple publications from overlapping study populations or the same study, only the one with the largest sample size was selected (Figure 1).


Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis.

Jin J, Hu C, Yu M, Chen F, Ye L, Yin X, Zhuang Z, Tong H - PLoS ONE (2014)

Flow diagram of study selection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061070&req=5

pone-0100206-g001: Flow diagram of study selection.
Mentions: To further assess the relationship between IDH1/2 mutations and MDS risk, we conducted a meta-analysis combining our study data with published studies on IDH mutations in MDS [3], [14], [15], [16], [17], [18]. Two independent reviewers (CH and MXY) performed a systematic literature search using ISI Web of Science, PubMed and the Cochrane Library for relevant papers published before December 2013 by the search term “(MDS OR myelodysplastic syndrome OR preleukemia OR myelodysplasia) AND (IDH1 OR IDH2).” Reviews and references of related articles were checked for missing information. Eligible papers met all the following criteria: (1) assessed the association between IDH1/2 mutations and outcomes in MDS; (2) detailed survival information of patients with IDH1 or IDH2 mutations; (3) reported the study in English. Animal studies, letters to the editor without original data, reviews and case reports were excluded. In the event of multiple publications from overlapping study populations or the same study, only the one with the largest sample size was selected (Figure 1).

Bottom Line: In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023).The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS.Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

ABSTRACT

Background: Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).

Methods: Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.

Results: In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.

Conclusion: The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.

Show MeSH
Related in: MedlinePlus