A Comparative Study Of The Clinical And Biological Characteristics Of Myelodysplastic Syndromes With Excess Blasts-2 And Acute Myeloid Leukemia With Bone Marrow Blast Percentage Of 20-30%

ObjectiveThe study is aimed to analyze the clinical and biological characteristics of patients with myelodysplastic syndromes with excess blasts-2(MDS-EB-2)and acute myeloid leukemia(AML)with bone marrow(BM)blast percentage of 20-30%in our hospital,and to compare the similarities and differences between them.MethodsThe clinical dates of 43 patients newly diagnosed as MDS-EB-2(Group EB-2)and50 patients diagnosed as de novo AML with BM blast percentage of 20-30%(Group AML)of Fujian Medical University Union Hospital from 01 January 2016 to 01October 2018 were analyzed retrospectively,and 11 cases in Group EB-2 transformed into acute myeloid leukemia(Group MDS/AML).Group A were risk-stratified by the Revised International Prognostic Scoring System(IPSS-R),Group B were risk-stratified by the risk stratification of AML based on the European LeukemiaNet(ELN).Clinical features,laboratory examinations,therapeutic regimens,survival states of both two groups were analyzed and compared.Results1.Group EB-2:(1)Analysis of clinical characteristics There were 43patients in total,including 27 males and 16 females,the ratio of man to female is 1.69 to1,the median age is 63.Among them,13 cases were transformed to acute leukemia,11cases were converted to AML,1 case was converted to ALL,and 1 case was not examined by bone marrow aspiration after transformed.At the end of follow-up,31patients died,8 survived and 4 lost.All patients presented with different degrees of anemia,infection or hemorrhage,and anemia is the main reason for consultation.There were 8 patients had splenomegaly(19.05%).23 cases were complicated with chromosomal abnormalities(63.89%).Grouped by IPSS-R,there were 15 cases in high-risk group and 28 cases in extremely high-risk group.There were 30 cases received at least one course of DAC in our hospital,18 cases's ages were not less than60 years old.Among them,8 cases received demethylation therapy not more than 2courses,with a median OS of 4.0 months,10 cases received demethylation therapy more than 2 courses,with a median OS of 14.0 months;12 cases of them under 60 years old.Among them,6 cases received demethylation therapy not more than 1 course,with a median OS of 4.0 months,6 cases received demethylation therapy more than 1 course,with a median OS of 10.0 months.13 cases received supportive treatment only,12patients were over 60 years old,the median OS was 1.13 months,1 patients were under60 years old,and were lost.(2)Analysis of factors affecting survival The median OS of 43 patients of group EB-2 were 7.0 months(rage:1.376-12.624months),the univariate analysis showed that:stratified into extremely high-risk group through IPSS-R,combined trilineage reduction,elevated LDH,bone marrow hyperplasia<50%,and combined with abnormal location of immature precursor cells(ALIP)and not treated with DAC had shorter OS.Multivariable analysis showed that:The combination of bone marrow ALIP and untreated with DAC were independent adverse factors affecting the prognosis of MDS-EB-2.2.Group AML:(1)Analysis of clinical characteristics There were 50 patients in total,including 31 males and 19 females,the ratio of man to female is 1.63 to 1,the median age is 57.5.At the end of follow-up,20 patients died,18 survived and 12 lost.All patients also presented with different degrees of anemia,infection or hemorrhage.17 patients had splenomegaly(42.5%).14 cases were complicated with chromosomal abnormalities(38.89%).According to the genetic risk stratification of the European Leukemia Network(ELN)in 2017,there were 3 cases with good prognosis,12 cases with moderate prognosis and 27 cases with poor prognosis.There were 31 cases received chemotherapy or demethylation therapy in total:8 cases's ages were not less than 60 years old.Among them,6 cases received chemotherapy not more than 2 courses,with a median OS of 2.0 months,2 cases received demethylation therapy more than 2courses,with a median OS of 3.67 months;23 cases of them were under 60 years old.Among them,6 cases received demethylation therapy not more than 1 course,with a median OS of 13.0 months,17 cases received demethylation therapy more than 1 course,with a median OS of 27.5 months.19 patients received best the supportive treatment.The median OS was 1.5 months in 15 patients over 60 years old,and 4 patients were younger than 60 years old,with a median OS of 0.5 months.(2)Analysis of factors affecting survival The median OS of 50 patients of group AML were 12.0 months,the univariate analysis showed that:Age?60 years old,WBC?25×10~9/L,elevated LDH,combined with myelofibrosis(MF),stratified into poor prognosis by the genetic risk stratification of ELN in 2017,received only supportive treatment,no remission after initial induction had shorter OS.Multivariable analysis showed that:no remission after first induction therapy was the independent adverse factors affecting the prognosis of AML.3.Group transformed:Analysis of clinical characteristics There were 11patients in total,including 9 males and 2 females,the ratio of man to female is 4.5 to 1,the median age is 63,the main types were M2 and M5,the median time to turn was 10months.At the end of follow-up,all 11 patients died,the total OS was 10.5 months,the median OS after turn was 3.5 months.All patients were treated with DAC.Turn stage:All patients presented with anemia,infection and bleeding.Only 1 case had elevated leukocyte count(9.09%);10 cases had decreased granulocyte count(90.91%),4 cases had deficiency of granulocyte(36.36%);4 cases had blast cells>30%,7 cases had blast cells<30%;3 cases had splenomegaly(30.00%).4.Group EB-2 and Group AML:(1)Comparison of clinical characteristics:The two groups were similar in clinical manifestations such as gender,anemia,thrombocytopenia,elevated LDH and gene mutation rate(P>0.05),and there was no significant difference in OS(P>0.05),but Group EB-2 was older than Group AML(P=0.032),more prone to granulocytosis(P=0.047)and chromosomal abnormalities(P=0.034),but less prone to splenomegaly(P=0.025)and peripheral hyperleukocytosis(P<0.0001).(2)Comparisons between treatment and OS:In patients over 60 years old,OS of Group EB-2 treated with demethylation was similar to that of Group AML treated with chemotherapy(P>0.05),and OS of patients with supportive treatment was not significantly different(P=0.949);In patients younger than 60 years old,OS of Group AML treated with>1 course of chemotherapy was significantly higher than that of Group EB-2 treated with>1 course of demethylation(P=0.004),while the OS of Group EB-2 treated with?1 course of demethylation was similar to than that of Group AML treated with?1 course of chemotherapy(P=0.062).5.Group MDS/AML and Group AML:(1)Comparison of clinical characteristics:The counts of WBC after turned in Group MDS/AML was significantly lower than that in Group AML(P=0.020),but the BM primordial cells were significantly higher(P<0.0001).The part of Group MDS/AML whose BM primordial cells were20-30%has similar gender,age,number of granulocytes,anemia,thrombocytopenia,splenomegaly,chromosome karyotype and gene abnormalities with Group AML(P>0.05).(2)Comparisons between OS:The OS after turned of Group MDS/AML was significantly shorter than that in Group AML(P=0.026),but OS of the the part of Group MDS/AML whose BM primordial cells were 20-30%has not significantly different from that of AML group(P>0.05).6.The effect of DNMT3A gene mutation on OS in EB-2 group and AML group:there were 3 cases in Group EB-2,the median OS 14.0 months,and 3 cases in Group AML,the median OS 1.5 months.There was significant difference between the two them(P=0.025).Conclusion1.There are similar clinical manifestations of sex,anemia,thrombocytopenia,elevated LDH,gene mutation rates and OS of MDS-EB-2 and Acute Myeloid Leukemia with Bone Marrow Blast Percentage of 20-30%;However,MDS-EB-2 patients are mostly elderly,and are more prone to granulocyte deficiency and chromosomal abnormalities,as well as less prone to splenomegaly and peripheral hyperleukocytosis.2.Once MDS-EB-2 turn to AL,they may be more dangerous than Acute Myeloid Leukemia with Bone Marrow Blast Percentage of 20-30%,but the clinical biological indexes and survival time of the part of AML transformed from MDS whose BM primordial cells were 20-30%were similar to that of Acute Myeloid Leukemia with Bone Marrow Blast Percentage of 20-30%.3.In patients not younger than 60 years old,the OS of MDS-EB-2 and Acute Myeloid Leukemia with Bone Marrow Blast Percentage of 20-30%is similar.In patients younger than 60 years old,the OS of Acute Myeloid Leukemia with Bone Marrow Blast Percentage of 20-30%treated with>1 course of chemotherapy was significantly higher than that of MDS-EB-2 treated with>1 course of demethylation.4.The mutation of DNMT3A gene may be involved in the pathogenesis of MDS and AML,and may play different roles in the progression of the two diseases,and is more malignant in AML.