| Background:Myelodysplastic syndrome(MDS)and acute myelogenous leukemia(AML)are heterogeneous groups of clonal hematopoietic diseases,characterized by low hematopoietic efficiency and proliferation of leukemia cells;In such diseases there is widespread bone marrow suppression,including severe thrombocytopenia,which is the main cause of death in most patients with MDS and AML.In 2012,thrombocytopenia was included in the revised International Prognostic Scoring System(IPSS-R)as an independent predictor of poor prognosis for MDS.DCAG has achieved definite clinical efficacy in the treatment of intermediate and high risk MDS and low-proliferative or senile AML,but the main side effect of this regimen is severe,long-term thrombocytopenia after chemotherapy,and clinical platelet transfusion is difficult,severe thrombocytopenia has brought great harm to the patient’s life,thrombopoietin receptor agonists have shown the effectiveness and safety of promoting platelet recovery in a variety of diseases with thrombocytopenia.Objective:To study the recombinant human thrombopoietin to promote the recovery of platelets in DCAG-treated patients with high-risk myelodysplastic syndrome/low-proliferative acute myeloid leukemia,and to evaluate the significance of promoting platelet recovery.Method:The multi-center clinical trial method began on May 31,2018,and ended on October 31,2019,at the Henan Provincial People’s Hospital,Luoyang Central Hospital Affiliated to Zhengzhou University,Luohe Central Hospital,First People’s Hospital of Xinxiang City,and First Affiliated Hospital of Henan University of Science and Technology and other hospitalsused the DCAG regimen to treat 100cases of intermediate and high risk MDS and low-proliferative AML.According to the random 1:1 ratio,it was divided into test group and control group,50 cases each.The test group was treated with DCAG+rhTPO,and rhTPO was started when the platelet was below 30×10~9/L after chemotherapy,the dosage was 300ug/Kg,it was discontinued when the platelet was stable above 50×10~9/L,when the platelet was below 20×10~9/L platelet transfusion treatment was given;The control group was given DCAG+blank control,and platelet transfusion treatment was given when platelets were lower than 20×10~9/L.Comparing the general clinical characteristics of the two groups of patients(age,gender,whether they have underlying disease,white blood cells,hemoglobin and platelets at the initial diagnosis,type of disease,IPSS-R grouping,bone marrow blast cell ratio,dysplasia,chromosome karyotype),time required for platelet recovery to 20×10~9/L,30×10~9/L,50×10~9/L and 100×10~9/L nodes,the length of hospitalization during treatment(excluding patients who had increased hospitalization due to infection),numbers of platelet transfusion,bleeding scores(refer to 2016 edition ITP bleeding scores),remission,overall survival time and influencing factors,disease progression-free survival time to evaluate the significance of rhTPO to promote platelet recovery in patients with DCAG-treated intermediate and high risk MDS and low-proliferative AML.Result:1.There are no significant differences in general clinical characteristics between the two groups of patients(P>0.05),and the two groups of patients are comparable.Comparing the recovery rate and time of platelets between the two groups,the time required for platelet stability to be higher than 20×10~9/L,30×10~9/L and 50×10~9/L are significantly better in the rhTPO test group than in the control group(respectively:6.48±2.15 days vs.8.38±3.07 days,9.02±2.73 days vs.12.24±3.92 days,12.43±4.67days vs.15.48±9.28 days),the results have significant statistical differences(P<0.05).The time required for platelet recovery to the node of 100×10~9/L is not statistically significant(20.81±11.21 days vs.23.00±19.82 days,P=0.069).The numbers of platelet transfusion in the rhTPO test group is significantly lower than that in the control group(4.41±3.06U vs.6.06±4.01U,P=0.047),the difference is statistically significant.In the length of hospitalization for each course of treatment(excluding patients who had increased hospitalization due to infection),the test group(n=39)less than the control group(n=37)(22.02±5.92 days vs.28.54±7.70 days,P=0.043),the result has significant statistical differences.2.Referring to the 2016 version of the ITP bleeding scores,the scores of the rhTPO test group:0point:37 cases,1 point:8 cases,2 points:4 cases,3 points:1 case;the control group 0 point:27 cases,1Point:8 cases,2 points:7 cases,3 points:8 cases.The rhTPO test group was significantly lower than the control group on the 2 and 3 points,and the bleeding scores between the two groups show significant statistical significance(P=0.045).3.Comparing the remission between the two groups,6 cases(12.0%)had complete remission(CR),5cases(10.0%)had partial remission(PR),and 27 cases(54.0%)had morrow complete remission(mCR),hematological improvement(HI)4 cases(8.0%),non-remission(NR)8 cases(16.0%),the overall response rate(ORR)=CR+PR+mCR+PR=84.0%;the control group CR 4 cases(8.0%)),mCR 29 cases(58.0%),PR 2 cases(4.0%),HI 5 cases(10.0%),NR 10 cases(20.0%),ORR=80.0%.Both groups of patients achieved a higher overall response rate,there is no significant statistical significance between the two in terms of remission(P=0.466).4.Comparison of adverse reactions,the main adverse reactions were bone marrow suppression and infection,and both groups of patients had grade III-IV bone marrow suppression.16 patients(32.0%)were infected in the test group:including 11 cases of lung infection(22.0%),1 case of oral infection(2.0%),2cases of bacteremia(4.0%),and 2 cases of upper respiratory tract infection(4.0%).The control group infected 14 cases(28.0%),including 8 cases of lung infection(16.0%),oral infection 1 case(2.0%),bacteremia 2 cases(4.0%),perianal infection 2 cases(4.0%)),1 case of urinary tract infection(2.0%);The second adverse reactions were liver function damage and gastrointestinal reaction,in the test group,4 cases(8.0%)had significant liver function damage(transaminases increased more than 2 times the normal value),and 3 cases(6.0%)in the control group;15 cases(30.0%)with gastrointestinal reactions in the test group,17 cases(34.0%)in the control group.When adverse reactions occurred in both groups of patients,symptomatic support treatment was given,and no serious adverse events occurred.Statistical analysis compared the incidence of adverse reactions between the two groups,and there is no significant difference between the two groups(P>0.05).5.The overall survival time(OS)and disease progression-free survival time(PFS)were compared between the two groups.Follow-up to 2020.02.29,the test group died of 18 cases,2 cases were lost to follow-up due to disease progression,30 cases were survived,28 cases died in the control group,3 cases lost to follow-up,19 cases were survived.The median OS of the test group was 29 months(95%CI:17.173-40.863),and the median OS of the control group was 24 months(95%CI:19.973-28.027),there is a statistically significant difference in the overall survival time(P=0.009).The two groups of patients also showed significant statistical difference in the median disease progression-free survival time(P=0.004):the median PFS of the test group was 24 months(95%CI:20.790-35.210),and the median PFS of the control group 21 months(95%CI:15.348-26.652).The results of univariate analysis showed that the type of disease and karyotype of chromosome may be risk factors affecting the overall survival time of patients,while the results of multivariate analysis showed that the patient’s age,karyotype of chromosome and the recovery time of PLT to 20×10~9/L may be risk factors affecting the overall survival time of patients.Conclusions:1.rhTPO can make platelet recovery faster in patients treated with DCAG regimen,reduce the risk of bleeding,reduce the numbers of platelet transfusion and the length of hospitalization2.Although rhTPO cannot improve the overall response rate of patients,it can make patients obtain longer OS and PFS3.rhTPO does not increase the incidence of adverse reactions to treatment,and can safely and effectively promote platelet recovery4.Chromosome karyotype,age,and time of PLT recovery to 20×10~9/L affect the overall survival time of patients and are prognostic risk factors... |
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