Clinical Analysis On Intermediate To High Risk Myelodysplastic Syndrome Patients Treated By Low Dose Decitabine

Objective: To evaluate the efficacy and safety of low dose Decitabine in the treatment of intermediate to high risk MDS. And to explore the factors that affecting the treatment effect of intermediate to high risk MDS patients treated by low dose Decitabine.Methods: Collect the clinical data of patients from November 2012 to November 2015. There were 38 patients who was clearly diagnosed as MDS by the bone marrow cytology, bone marrow biopsy, genetics and chromosome examination in the first affiliated hospital of Zhengzhou University. According to the International Prognosis Scoring System(IPSS), all patients should have a score of 0.5 or higher. Each patient should achieved at least one course of treatment and relevant laboratory examination results are necessary to evaluate the curative effects. The patients including 27 male and 11 female. The age range from 20 years to 80 years and the media age here was 50 years old. 18 patients were intermediate 1 risk, 9 patients were intermediate 2 risk and another 11 patients were high-risk according to the IPSS. There were 12 patients examined the HLA-DR 15 allele expression. 4 patients showed HLA-DR 15 allele positive and another 8 patients showed HLA-DR 15 allele negative. A total of 38 patients, on the basic of routine treatment, were treated with Decitabine at a dose of 15mg/m2 by continuous intravenous infusion for 1 hour, and repeated daily from thefirst day to the fifth day. The cycle was repeated every four weeks. Evaluate the efficacy and analyze the factors that affecting the treatment effect. Record the adverse reactions after every cycle of therapy and follow-up the patients’ survival.Results:(1) 38 patients achieved a total of 115 courses treatment. 9 patients received one course, 12 patients received two courses, 5 patients received three courses, 5 patients received four courses, 3 patients received six courses, 3 patients received seven courses and 1 patient received eight courses of Decitabine treatment. The median course was 2 with a range of 1 to 8. And the average course was 3.02.(2) The overall response rate was 73.68%, the responses included complete remission(n=10, 26.32%), marrow complete remission(n=6, 15.79%) and hematologic improvement(n=12, 31.57%). 4 patients showed HLA-DR 15 allele positive and the incidence rate was 33.3%. 1 of them achieved CR(25%) and 2 patients achieved hematologic improvement(50%). The overall response rate was 75%. In a total of 10 patients who achieved CR, 1 patient achieved CR in the first course, 3 patients achieved CR in the second course, 5 patients achieved CR in the third course and 1 patient achieved CR in the fourth course. The median course for achieving CR was 3 courses.(3) Univariate analysis showed that patients with different age, different sex, different chromosome karyotype prognosis, different WHO classification, different IPSS groups and different duration from diagnose to start treatment, was or not achieved other treatments, was or not red blood cell transfusion-dependency or platelet transfusion-dependency and the count of bone marrow blasts at diagnosis didn’t affect the overall response of low dose Decitabine in the treatment of intermediate to high risk MDS(P>0.05).(4) In a total of 115 courses, Grade III-IV anemia rate was 37.39%(43/115), grade III-IV neutropenia rate was 40.87%(47/115), grade III-IV thrombocytopenia rate was 40.00%(46/115). Grade III-IV anemia rate in the first 3 courses was significantly and statistically different with that in the followed 5 courses(46.43% vs 12.90%, P<0.05). Grade III-IV neutropenia rate in the first 3 courses was significantly and statistically different with that in the followed 5courses(48.81% vs 19.35%, P<0.05).Grade III-IV thrombocytopenia rate in the first 3 courses was significantly and statistically different with that in the followed 5 courses(52.38% vs 6.45%, P<0.05). Grade III-IV infection rate was 17.39%(20/115). Grade III-IV infection rate in the first 3 courses was significantly and statistically different with that in the followed 5 courses(22.62% vs 3.23%, P<0.05). Grade III-IV bleeding rate was 1.74%(2/115). 3 patients died during the bone marrow suppression period. No one stopped treatment due to the adverse reactions. No patient died within 30 days.(5) Due to the last follow up at 2015.11.30, 3 patients were lost to follow up, 4 died, and 31 patients still alive. The median follow-up duration was 12 months and the media overall survival time was 14.3 months. The one year survival rate was 52.1%.Conclusion: 1. Low-dose Decitabine is effective in the treatment of intermediate to high risk MDS. And the median response course is three. There is a relative lower risk of severe adverse events. It mainly occur in the first three courses. 2. Patients who achieved response from the low dose Decitabine treatment should continue to accept treatment. 3. Patients who are HLA-DR15 positive may benefit from the treatment of low dose Decitabine. 4. Patients with different age, different sex, different chromosome karyotype prognosis, different WHO classification, different IPSS groups and different duration from diagnose to start treatment, was or not achieved other treatments, was or not red blood cell transfusion-dependency or platelet transfusion-dependency and the count of bone marrow blasts at diagnosis didn’t affect the overall response of low dose Decitabine in the treatment of intermediate to high risk MDS.