Clinical Efficacy Of Low-dose Decitabine Combined With Cytarabine In The Treatment Of Patients With High-risk MDS

Background and purpose:myelodysplastic syndromes(MDS)are heterogeneous clonal hematopoietic neoplasms characterized by ineffective hematopoiesis,peripheral blood cytopenias,and a risk of progression to acute myeloid leukemia(AML).For more than a decade,demethylation drugs azacitidine and decitabine have been the main treatments for myelodysplastic syndrome,but the failure of demethylation drugs is common.Cytarabine and decitabine are both deoxycytidine analogues,but the anti-tumor mechanism of the two drugs is different,combination of cytarabine and decitabine is a promising strategy for the treatment of MDS.In view of the fact that MDS patients are elderly,often complicated with medical comorbidities,and have poor tolerance to adverse drug toxicity,and the main adverse events of cytarabine and decitabine are myelosuppression,using of standard dose of decitabine combined with cytarabine will increase the risk of hemocytopenia、bleeding and infection that may cause death.The purpose of this study was to observe the efficacy and safety of low dose of decitabine combined with cytarabine in the treatment of high-risk MDS,and compare the regimen with the recommended dose of decitabine,so as to provide evidence for the choice of treatment for patients with high-risk MDS.Methods: thirty-three patients with high-risk MDS in the First Affiliated Hospital of Guangxi Medical University were analyzed retrospectively,including 15 patients in the group treated with decitabine combined with cytarabine and 18 patients in the group treated with decitabine alone.The differences in overall response rate,continuous response duration and progression-free survival time between the two treatment groups were compared,and the safety of the two regimens was evaluated.Results: the ORR of the combination group and the monotherapy group was 73.3% and 66.7% respectively;the CR rate was 20.0% and 27.8%respectively,the erythroid response rate was 60% and 50% respectively,and the platelet response rate was 60% and 38.7% respectively.There was no statistical difference in ORR,CR rate,erythroid response rate and platelet response rate between the two groups.Among the 11 patients who responded to the treatment in the combination group,5 patients were still in continuous response at the end of the follow-up,and the median response duration was 8.5 months[95%CI=7.256,9.744].The median progression-free survival time was 12.0months [95% CI= 8.995,15.005].All the 12 patients in the monotherapy group had relapsed or progressed at the end of the follow-up.The median response duration was 6.0 months [3 ～ 14 months],and the median progression-free survival time was 7.5 months [4.0 ～ 15.0 months].There were significant differences in median response duration(P= 0.047)and median progression-free survival tine(P=0.038)between the two groups.Conclusions: 1.Low-dose decitabine combined with cytarabine in the treatment of high-risk MDS has high overall response rate,platelet response rate and erythroid response rate,which can reduce blood transfusion.And the combination regimen is safe and well tolerated.2.Compared with the generally recommended dose regimen for MDS,reduced dose of dexitabine combined with cytarabine could not improve the overall response rate,but could prolong the response duration,delay the recurrence of the disease,and did not increase the incidence of hematological adverse events and infection.