Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome.

Koung Jin Suh,Inho Kim,Junshik Hong,Jinny Park,Yoo Hong Min,Youngil Koh,Chu Myoung Seong ,Dong Yeop Shin ,Jae Hoon Lee ,Jae Sook Ahn ,Sung Soo Yoon ,Byung Soo Kim ,Yun Gyoo Lee ,June Won Cheong ,Soo Mee Bang ,Hyeoung Joon Kim ,Yeo Kyeoung Kim ,Yeung Chul Mun ,Yong Park ,Jeong-Ok Lee ,Sung Yong Kim ,Hong Ghi Lee

doi:10.1371/journal.pone.0166245

Abstract

Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment.

Highlights

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective haematopoiesis resulting in bone marrow (BM) failure and increased risk of transformation to acute myeloid leukaemia (AML) [1]
Chromosomal translocations are rare in MDS, whereas other chromosomal abnormalities such as losses and gains of genetic material are detected in half of all patients with MDS
We excluded patients with secondary MDS, chronic myelomonocytic leukemia (CMML), and patients with AML and a BM blast count of 20–30% who were classified as having refractory anaemia with excess blast (RAEB)-t according to the French-American-British classification [12]

Summary

Introduction

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective haematopoiesis resulting in bone marrow (BM) failure and increased risk of transformation to acute myeloid leukaemia (AML) [1]. Owing to recent advances in technologies such as whole genome sequencing, recurrent mutations in splicing factor (e.g., SF3B1 and U2AF1) and epigenetic regulator (e.g., TET2, ASXL2, DNMT3A, EZH2, and IDH1/2) genes have been identified as the predominant molecular mechanism underlying the pathogenesis of MDS [4,5,6]. Since the identification and reporting of recurrent chromosomal translocations are essential to provide insights into the mechanisms of pathogenesis and identify genes involved in the pathogenesis of MDS, the role of cytogenetics including the study of genomic structure and function will remain important. Novel and recurrent translocations have been reported in a large series of patients [7,8]; only a few studies have addressed the prognostic impact of chromosomal translocations [9,10,11]

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