| BackgroundPrimary immune thrombocytopenia(ITP)is a type of acquired and hemorrhagic disease which mainly presents with thrombocytopenia and increased risk of bleeding.The course of the disease is prolonged and prone to relapse,and it is still difficult for some patients to control the platelet level within the safe range after the current first-and second-line drug treatment.Recent studies have found that abnormal DNA methylation exists in ITP patients,which affects the differentiation,development and function of bone marrow megakaryocytes,Tregs,Th and other immune cells,and thus directly or indirectly leads to decreased platelet generation and increased damage.Decitabine(DAC)is a specific DNA methyltransferase inhibitor with demethylation effect at low dose.At present,they are mainly used in myelodysplastic syndrome(MDS),which can effectively improve the level of platelets in MDS patients.Elevated platelets were also observed in the treatment of sickle cell anemia,thalassemia and solid tumors,with good safety.Recent laboratory studies have found that low doses of DAC promote megakaryocyte maturation and increase platelet release.The above research and findings provide sufficient theoretical support for the treatment of primary immune thrombocytopenia with a small dose of decitabine.ObjectiveTo investigate the initial remission,long-term remission and safety of low-dose decitabine in the treatment of primary immune thrombocytopenia.MethodsAll subjects were enrolled in strict accordance with inclusion criteria and exclusion criteria.Drug regimen:Decitabine at 3.5 mg/m2 intravenously for 3 days per cycle for 3 cycles with a 3 to 4-week interval Concomitant therapy:Platelets can be injected if severe active bleeding occurs.No concomitant therapy:Any other effective treatment for ITP.Follow-up:The patients were followed up once a week for the first 4 weeks,once every 2 weeks for the 8th to 12th weeks,and once a month thereafter.Those who were effective were followed up until recurrence,and those who were ineffective or relapsed were followed up for at least 6 months to evaluate the safety.Platelet count,bleeding symptom,liver and kidney function and adverse events were recorded at each follow-up to evaluate the efficacy and safety of the drug.Study end points:The primary end points were complete response,response,no response,loss of CR or R,and bleeding scores.Secondary end-points included time to response(TTR),duration of response and adverse events.ResultsA total of 65 ITP patients admitted to Qilu hospital from September 2015 to August 2018 were included in this study.There were 28 males and 37 females,with a median age of 41(18-75)years and a median duration of ITP was 6(1-348)months.Median baseline platelet count before treatment was 9(0-29)109/L,and median bleeding score before treatment was 1(0-4).After at least 3 cycles of low-dose decitabine treatment,a total of 27 patients achieved initial remission,with an OR rate of 41.5%(27/65),CR rate of 18.5%(12/65)and R rate of 23.0%(15/65),respectively.The median time to response was 28(4-84)days,and the median duration of response 15(1-41)months.To the end of follow-up,10 patients relapsed,and 17 patients maintained sustained response,with a sustained response rate of 24.6%.Among the 27 patients with initial remission,the 25 patients who were followed up for 1 year had a relapse free survival rate of 87.5%(21/24),75.0(18/24),66.7%(16/24)and 62.5%(15/24)in 3m,6m,9m and 12m respectively.Among the 12 patients who were followed up for 2 year,the relapse free survival rate were 83.3%(10/12),58.3%(7/12),41.7%(5/12)and 41.7%(5/12)in 6m,12m,18m and 24m,respectively.After a follow-up of 3 years,2 patients with initial remission achieved sustained remission,and the platelet level remained at>100 × 109/L until the end of this follow-up.Most patients showed significant improvement in bleeding symptoms after treatment.Three relapsed patients received the second or third course of low-dose decitabine treatment again,with 1 patient receiving R and 2 patients receiving CR.Adverse effects were observed in 12 patients,including nausea in 4 patients,low fever in 2 patients,mild elevation of transaminase in 3 patients,and diarrhea in 2 patients,all of which presented mild symptoms and returned to normal after symptomatic treatment.ConclusionThe low-dose decitabine in the management of ITP yields high initial remission rate and long-term remission rate with good tolerance and high safety,and retreatment after relapse is still effective.It is expected to become a promising choice for ITP treatment. |
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