Clinical Efficacy Observation Of Thalidomide Reduction In Maintenance Treatment Of Patients With Non-Transfusion-Dependent Thalassemia

Objective:Explore the optimal dosage of thalidomide in the treatment of non-transfusion-dependent thalassemia(NTDT)patients,and observe the clinical efficacy and toxic side effects of thalidomide on NTDT after reducing the dose of thalidomide.Methods:A total of 23 patients with NTDT who were treated with thalidomide 50 mg/d were enrolled,and a total of 2 phases of the study were carried out using self-control methods.In the first phase,the dose of thalidomide was reduced to 25 mg/d for a total of 3 month.The general information of the patients was recorded at the time of enrollment,including genotype,age of onset,and whether the spleen was cut.Before the start of the test,the patients were screened for blood routine,liver and kidney function,and serum ferritin(SF).Female patients were checked for urine human chorionic gonadotropin(HCG);during the trial,the patients were followed up monthly for blood routine and liver Changes in renal function,while recording adverse drug reactions during medication.At the end of the follow-up,in addition to the routine follow-up content,the female patient rechecked the urine HCG.In the second phase of the trial,the dose of thalidomide was continuously reduced to 12.5 mg/d for 3 months,followed up once a month,and the content of the follow-up was the same as in the first phase.The results of various laboratory indicators during the treatment period of the patients were recorded.At the end of the first phase of the trial,each indicator was compared with the pre-reduction and baseline levels,and at the end of the second phase of the trial,the indicators were compared with the twice pre-reduction and corresponding baseline levels.Results:In the end,a total of 23 patients in the first phase,and a total of 14 patients in the second phase completed the study according to the experimental protocol.The results showed that the average hemoglobin(Hb)at the end of the two phases of follow-up was 3.0±1.5g/dL(P<0.001)、3.1±1.4g/dL(P<0.001)higher than the corresponding baseline level.There is no significant difference in the average Hb value between the first stage and the reduction dose(thalidomide 50mg/d),there is no significant difference in the average value of Hb between in the second stage and the twic recdudtion the thalidomide dose.Compared with the pre-reduction,the decrease value of Hb is less than lg/dL or the Hb level is higher than the pre-reduction,is defined as the maintenance of the efficacy,and the decrease exceeding lg/dL is defined as the unmaintainable efficacy.The rates of could be maintained efficacy were 87.0%and 71.4%after the two-stage follow-up.At the end of the first phase of follow-up,the patient’s red blood cell(RBC)count and reticulocyte(Ret)count were significantly higher than the baseline value,and there was no difference compared with thalidomide 50 mg/d.Aspartate aminotransferase(AST)was significantly lower than the baseline value(P<0.01),and there was no significant difference compared with thalidomide 50mg/d.Lactic dehydrogenase(LDH)was significantly lower than the baseline value and thalidomide 50mg/d(P<0.05),white blood cell(WBC)count,platelets(PLT),nucleated red blood cell(NRBC),total bilirubin(TBil),indirect bile Indirect bilirubin(IBil),Alanine aminotransferase(ALT),and Creatinine(Cr)had no significant changes compared with baseline values and before reduction dose.After the second stage,each index was compared with the corresponding baseline value and before the twice of reduction dose.RBC count,WBC count,PLT count,NRBC count,Ret count,LDH,TBil,IBil,ALT,AST,Cr were among the groups.There is no significant difference between them.During the 6-month follow-up,abdominal distension was observed in 1 patient,constipation occurred in 1 patient,which could be relieved after adjusting the diet,no peripheral neuropathy was observed,and no dose adjustment due to adverse reactions occurred in all patients.Correlation analysis showed the increase value in Hb in the first stage was significantly correlated with that the increase value in Hb which during the treatment with thalidomide 50 mg/d(r=0.852,P<0.001).The increase value in Hb in the second stage was significantly correlated with the increase value in Hb which during the treatment with thalidomide 50 mg/d(r=0.852,P<0.001)and 25mg/d(r=0.658,P=0.01).It has nothing to do with the patient’s age,gender,genotype,spleen cut,baseline Hb level,Ret count,NRBC count,and the cumulative use time of thalidomide 50 mg/d.Conclusions:For most NTDT patients,it is more likely that thalidomide can maintain the original efficacy after the dose is reduced,and there is still good safety and tolerability after the dose reduction.Therefore,for those who have received thalidomide 50mg/d NTDT patients with effective treatment could try to gradually reduce the dose,while maintaining the efficacy,delay the appearance of peripheral neuropathy caused by the cumulative dose,and reduce the incidence of peripheral neuropathy related to the increase in daily dose.