| Part I The analysis of correlation between methylation ofmi R-124 and prognosis of patients with myelodysplasticsyndromeObjective To investigate the correlation between micro RNA-124(mi R-124) methylation and the prognosis of patients with myelodysplastic syndrome(MDS).Methods A total of 56 specimens from de novo adult MDS patients were recruited in this research to assess the methylation level of mi R-124 by the technique of pyrosequencing analysis. Combined with patients’ clinical information, we analyzed the correlation between their characteristics including methylation levels of mi R-124 and outcomes of clinical observation after a median follow-up of 13.8(1.0 ~ 46.5) months.Results We found thatmi R-124 genes(MIR124-1, MIR124-2, MIR124-3) were methylated in MDS patients, with various methylation levels of 4.25(0.75 ~ 30.00)%, 25.38(10.75 ~ 82.25)% and 10.44(2.33 ~ 36.22)% respectively. Other than World Health Organization(WHO) classification, WHO-based Prognostic Scoring System(WPSS) score, marrow blast count, karyotype, mean corpuscular volume(MCV), methylation levels of mi R-124-2 and mi R-124-3 affectedthe overall survival(OS) significantly(P=0.002 and P=0.011, respectively) in univariate analysis. As for cumulative incidences of MDS evolution towards acute myeloid leukemia(AML), patients who were older(P=0.023) and with advanced WHO classification stage(P=0.003), higher WPSS score(P=0.001), higher marrow blast count(P<0.001), and high methylationlevel of mi R-124-2(P=0.001) progressed rapidly to AML. Furthermore, multivariate analysis demonstrated that hypermethylation of mi R-124-3was an independent factor of OS. Median survival of patients with hypermethylation of mi R-124-3 was significantly shorter than those withlow methylation(median: 13.8 vs. 28.1 months, P=0.011).Conclusion The methylation of mi R-124 is a prognostic factor of MDS, and mi R-124-3 may be a new therapeutic target in MDS.Part II Impact of decitabine therapy prior to allogeneic hematopoietic stem cell transplantation in higher-risk patients with myelodysplastic syndromeObjective To evaluate the outcomes of pre-tranplant therapy with decitabine in patients with higher-risk myelodysplastic syndrome(MDS).Methods We retrospectively reviewed the results of 77 patients with higher-risk MDS who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT) between July 2007 and June 2014. Treatments of decitabine alone or combined with chemotherapies prior to allo-HSCT were performed in 38 patients as HMA group, while 39 patients as control group with best supportive care(BSC) or conventional chemotherapies. The median cycles of decitabine alone, combined with chemotherapies in HMA group and conventional chemotherapies in control group were one(range 1 ~ 4), two(range 1 ~ 6) and one(range 1 ~ 23), respectively. There were no significant differences between the two groups in their age, gender, WHO subtypes, IPSS-R scores, blasts in bone marrow, types of transplant and conditioning regimens.Results The median follow-up of survivors was 22.4(range 6.1 ~ 85.7) months. A total of 52 patients were alive, thirty-one(59.6%) in HMA group and twenty-one(40.4%) in control. The 5-year estimates of overall survival(OS) and event free survival(EFS) between HMA and control groups were 83.6% ± 6.2%versus48.1% ± 8.9%(P=0.019) and 75.7% ± 7.7%versus35.1% ± 8.3%(P=0.013), respectively. The cumulative incidence of relapse and non-relapse mortality(NRM) were 8.0% ± 3.1% versus 22.0% ± 5.8%(P=0.456) and 16.4% ± 3.9%versus43.0% ± 7.0%(P=0.028), respectively. There were no significant statistic differences in engraftment and transplant-related comorbidities between two groups. It was demonstrated by univariate analyses that receiving hypomethylating agent(P=0.019) and induction therapy(P=0.007) followed by HSCT, age <44 y/o at the time of transplant(P=0.047) and serum ferritin level <1500ng/ml(P=0.010) were of significance in OS improvement. However, multivariate analyses showed only age ≥44 y/o and bone marrow blasts ≥5% were independent adverse factors associated with OS and EFS.Conclusion It is feasible that decitabine performed as a bridging therapy to allo-HSCT, which may offer advantages in survival improvement and relapse reduction. However, prospective and randomized clinical trials(RCT) remain in urgent need. |
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