| ObjectiveAcute myeloblastic leukemia(AML)is a kind of highly heterogeneous hematological malignancies,characterized by cell differentiation block and excessive proliferation and inhibition of apoptosis in immature leukemic cells.The clinical manifestations are anemia,hemorrhage,infection and infiltration.At present,the complete remission rate(CR)of AML is up to 60%~80%,but there are still20%~30%young adults and 40%~50%of senile AML will undergo induction therapy failure,and 50%~70%of patients will eventually relapse who had achieved CR,therate of second CR is only 25%~40%,the median survival period is not more than half a year.To overcome the drug resistance and disease relapse is the key to improve the therapeutic efficacy of AML.Studies have confirmed that leukemia stem cells(LSC)play an important role in the occurrence,development,drug resistance and disease relapse of AML.Jordan and other studies on acute myeloblastic leukemia stem cells have showed that CD123 is the specific surface antigen of these cells,while the normal hematopoietic stem cell surface does not express CD123.The CD34+CD123+cell subsets were implanted into the mice model of non-obese diabetes/severe combined immunodeficiency(NOD/SCID)to induce the AML.Some studies indicated that the high expression of CD123 is positively correlated with the high residual disease after treatment in acute leukemia patients,indicating adverse prognosis.With the application of the second generation sequencing technology,newly discovered genetic abnormalities constantly refines the risk stratification and directs the clinical decision.Since cytogenetic and molecular tests are relatively time-consuming,and about 40%of AML patients lack cloned abnormalities,it is important to explore the specific leukemia cell surface antigen associated with prognosis in order to make early risk stratification and guide the therapy.In this study,the clinical data of 365 patients with newly diagnosed AML(non-APL)were retrospectively analyzed to explore the clinical significance of CD123 expression in AML.Methods1.Materials:Three hundred sixty-five cases of AML(non-APL,M0~M7)patients diagnosed in department of hematology of the first affiliated hospital of Zhengzhou University from January 2015 to December 2016,including 216 cases of male patients,149 cases of female patients,and median age was 51 years old(13~88years old).All cases were carried out blood routine,biochemistry test,bone marrow puncture and other examinations.The diagnosis of AML and risk stratification criteria refer to China guidelines for diagnosis and treatment of the adult acute myeloblastic leukemia(non-acute promyelocytic leukemia)(2017 edition),the assessment of efficacy refer to Standard for diagnosis and treatment of hematologic diseases.Patients were followed up from the date of the diagnosis,and the survivors were followed up to January 1,2018.2.Research methods:The level of CD123 expression in bone marrow samples is detected by flow cytometry(FCM)from 365 newly diagnosed AML patients,and the positive rate of antigen expression>20%was defined as positive expression.AML patients with non APL were divided into CD123 positive group and CD123 negative group,and the expression of CD123 and its clinical characteristics were explored(age,sex,FAB type,peripheral blood count,lactate dehydrogenase,ferritin,proportion of bone marrow blast cells,cytogenetics,molecular biology)and therapeutic efficacy(total remission rate after 1 course of chemotherapy,relapse rate,induction of treatment of CR,total survival).3.Statistical analysis:Data was processed with SPSS 22.0,using arithmetic mean and standard deviation to describe symmetric distribution data.And asymmetric distribution data was described by median and interquartile range.Quantitative data was analyzed by t test or Wilcoxon rank test.Categorical data was analyzed by chi-square test or Fisher exact test.The Kaplan-Meier survival curve was plotted and the survival curves of each group were compared with Log-rank method or Breslow method.Cox regression was used to analyze the effects of multiple factors on prognosis.Statistical significance was defined as P below 0.05.Results1.The initial WBC counts were 23.3×10~9/L(0.5-247.5)(Z=3.119,P=0.002),lactate dehydrogenase 486.5 U/L(136-3620)(Z=2.657,P=0.008)and bone marrow blast 67.2%(19-96.4)(Z=3.810,P=0.000)in CD123 positive patients,which were higher than these in the CD123 negative group,the difference was statistically significant.2.After 1 course of induction chemotherapy,CD123 positive group CR rate was48.35%(44/91),CD123 negative group CR rate was 73.91%(102/138),the difference was statistically significant(?~2=15.506,P=0.000).In 146 cases of AML patients with CR,there were 48 relapse,the total relapse rate was 32.87%(48/114),the CD123positive group was 56.8%(21/37),CD123 negative group was 26.47%(27/102),and the difference was statistically significant(?~2=6.294,P=0.012).The CD123 positive group(average rank of 88.77)and negative group(average rank 75.54)had statistically significant differences in the number of courses for CR(Z=-2.21,P=0.027).In 229 patients undergoing regular chemotherapy and follow-up in our hospital,there were 19 cases of primary drug-resistant,the primary resistance rate of CD123 positive group was 10.99%(10/91),CD123 negative group was 6.52%(9/138),and the difference was statistically significant(?~2=1.438,P=0.230).3.Univariate analysis found that the age(>60 years),adverse prognosis karyotype and CD123 positive patients had lower CR rate.Patients'CD123 positive[OR=0.428(95%CI 0.210-0.875),P=0.02)]was independent risk factor by the multivariate analysis for CR in AML patients.4.Cox regression model multivariate analysis found that CD123 expression positivewasanindependentprognosticfactoraffectingpatientOS[OR=1.011(95%CI 1.000-1.022),P=0.048].Among different prognosis group,the median OS time of CD123 positive group was shorter than that of CD123 negative group,but the difference was not statistically significant(P>0.05).ConclusionCD123-positive AML patients are used to have higher tumor loads at diagnosis and are associated with inferior clinical outcomes with lower one-course CR rate and shorter of the OS in AML patients.The expression of CD123 is correlated with the mutation of FLT3-ITD gene. |
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