Clinical Efficacy and Prognostic Factors of Decitabine for Treatment of Myelodysplastic Syndrome

Abstract

To explore the clinical efficacy of decitabine for treatment of patients with myelodysplastic syndrome (MDS) and factors predicting the prognosis. The clinical data of 87 patients with MDS treated with decitabine were analyzed retrospectively. The hENT1 mRNA expression and TP53 gene mutation were detected by Q-PCR and gene target sequencing, respectively. The relationship of clinical characteristics and molecular indicators with the clinical response to decitabine was analyzed. In treatment for median 4 (2-17) courses, a total 51 patients (58.6%) showed therapeutic responses, including CR in 17 cases, PR in 12 cases, mCR in 9 cases, HI in 13 cases; 36 (41.4%) patients showed non-response. Univariate analysis showed that the patients with the complex karyotype, monosomal karyotype, chomosome 7 abnormality and Plt count doubling after 1 course treatment had a high CR rate, while the patients with relative high risk by IPSS (intermediate risk 2+ high risk), complex karyotype and Plt count doubling after 1 course had much more high overall remission rate (ORR). The expression level of hENT1 mRNA in MDS patients with response was significantly higher than that in patients without response ［(1.78±1.45 (2-△△Ct) vs 0.96±0.97 (2-△△Ct)(P= 0.002)］. Among 51 patients with therapeutic response, the expression level of hENT1 mRNA in CR group was higher than that in non-CR group ［(2.58±1.44 (2-△△Ct) vs 1.39 ±1.3 (2-△△Ct), P= 0.005)］. Among 52 patients in relative high risk (intermediate risk 2 +high risk), the median OS time of patients with high hENT1 mRNA expression was significantly longer than that of patients with low hENT1 mRNA expression (31 vs 12 months)(P<0.001). Among 87 patients received decitabine treatment, the TP53 gene mutation occured in 11 (12.6%) patients. The ORR in patients with TP53 mutation was high (P=0.04), moreover the patients with TP53 mutation more easily gained CR (P<0.001). Multivariate logistic regression model showed that the complex karyotype, Plt count doubling after 1 course treatment, TP53 mulation and high expression of hENT1 mRNA were the independent prognostic factors for predicting the CR after decitabine treatment. IPSS staging, complex karyotype, Plt count doubling after 1 course treatment and hENT1 mRNA expression, TP53 gene mutation can be used to predict the tharapeutic efficacy of dectitabine for treatment of MDS.