Hypomethylation Therapy Impact On Prognosis Of Myelodysplastic Syndromes With Cytogenetic Abnormalities

Objective To evaluate the efficacy and prognosis of hypomethylation(decitabine)in the myelodysplastic syndrome(MDS)patients with abnormal chromosomal karyotype.Methods All the patients receiving decitabine treatment were divided into three groups according to the IPSS-R cytogenetic risk stratification by karyotype as follows: Group 1 was more favorable,including very good and good;Group 2 was intermediate;and Group 3 was more unfavorable,including poor and very poor.The clinical efficacy and prognosis of three groups were analyzed and compared.The leukemia transformation rate,overall survival were analyzed by Kaplan-Meier and Log-rank test.Results The overall response rate(ORR)in the Group 1was69.0%,including complete remission(CR)in 6 patients(20.7%),partial response(PR)in 5 patients(17.2%),hematologic improvement(HI)in 9 patients(31%).The complete cytogenetic response(c CR)was20%;The ORR in the Group 2was 55.6%,,including CR in 3 patients(16.7%),partial response in2 patients(11.1%),HI in5 patients(27.8%).The c CRwas22.2%.The ORR in the Group 3was 87.5%,including CRin 10 patients(62.5%),HI in4 patients(25%).The c CRwas56.3%.The Group 3 showed a statistically significant higher CR rate than Groups 1 and 2(P=0.005;P=0.006),and the cytogenetic CR rate in Group 3 was higher than in Group 1and Group2(P=0.056;P=0.033).The Group 3 were assigned to two groups including one group with chromosome 7 aberrance and the other group without chromosome 7 involvement,those carrying chromosome 7 aberrance showed a higher clinical CR and cytogenetic CR rate than the other patients,and the P values were 0.210 and 0.018,respectively.15 of the 63 patients(23.8%)were transformed to acute leukemia.In Group 1,10.3% were transformed to acute leukemia,and the median time was10(8-12)months;In Group 2,27.8% were transformed to acute leukemia,and the median time was 7(5-18)months;In Group 3,43.8%were transformed to acute leukemia,and the median time was 2(1-18)months.22 cases of the 63 MDS patients died(34.9%),and 41 cases survived(65.1%).The mortality rate of the 1 group was31.0%;The mortality rate of the 2 group was33.3%;The mortality rate of the 3 group was43.8%.Median OS of the three groups were 18.5(2-44)months,12.0(1-55)months,17.0(2.5-24)months.The probability for survival at 24 months was 80%,48%and 61% in the three groups,respectively.The probability for survival at 48 months was 56%,46%and 34% in the three groups,respectively.The Group 3 had OS comparable with Groups 1(17.0vs.18.5??,P=0.228).To analyze the effect of the cytogenetic response on OS,thirty-nine patients carrying a pre-existing abnormal chromosome were divided into response group and no response group according to the complete cytogenetic response.The patients who achieved a complete cytogenetic response presented a statistically significant longer survival than those who did not achieve a complete cytogenetic response after decitabine treatment(19vs.9??,P=0.020).The statistical difference of the OS was significant in the group of thrombocytopenia,number of courses and the curative effect(respectively,P=0.019,P=0.024 and P= 0.032).The results showed that the thrombocytopenia,Cytogenetic risk stratification and the curative effect could affect the prognosis,respectively,P=0.002 Exp(B)6.131,P=0.011 Exp(B)2.448 and P=0.003 Exp(B)0.113,by multivariable COX regression analysis.Conclusions The patients carrying more unfavorable karyotypes achieved better clinical and cytogenetic response than those with intermediate or more favorable karyotypes.Among the patients with poor or very poor karyotypes,those carrying chromosome 7 aberrance showed a better treatment response than the other patients,suggesting that the chromosome 7 involvement instead of the number of abnormalities predicted treatment response to decitabine.The patients with more unfavorable karyotypes could achieve survival comparable to that of the patients with more favorable karyotypes after decitabine treatment.Longer median OS were observed in the patients who achieved a complete cytogenetic response than in those who did not.Decitabine can overcome the poor prognosis of MDS patients with the poor chromosome karyotypes.The results showed that the thrombocytopenia,Cytogenetic risk stratification and the curative effect could affect the prognosis.The chromosome abnormality has prognostic value in MDS.