Clinical Study Of Core Binding Factor Acute Myeloid Leukemia

?.Clinical and laboratory characteristics of a single-center 416 core binding factor acute myeloid leukemia(CBF-AML)patients.ObjectiveTo retrospectively analyze the clinical,laboratory,cytogenetic and molecular biological characteristics of patients with core binding factor acute myeloid leukemia(CBF-AML)who were diagnosed and hospitalized in the first affiliated hospital of Soochow university from January 2010 to June 2017,to understand the clinical and laboratory characteristics of the CBF-AML patients in our center.MethodWe collected the clinical information of patients with CBF-AML who were diagnosed and hospitalized in the First Affiliated Hospital of Soochow University from January 2010 to June 2017.A total of 416 primary CBF-AMLs were included in the analysis,excluded cases of secondary hematological malignancy.Details,such as gender,age,peripheral blood cells count,percent of blast cells in bone marrow,morphology,flow immunity subtypes,karyotype,fusion genes,gene mutations were reviewed and compared within cytogenetic groups.Results1.A total of 416 patients with primary CBF-AML were included in the analysis.According to cytogenetical abnormality,t(8;21)/AML1-ETO accounted for 68%(283/417),inv(16)/CBFp-MYH11 accounted for 32%(133/417).The radio of male to female was(male:female=1.68:1)and the median age was 33 years old(range 7 to 71 years old).2.The level of peripheral white blood count(WBC)in the AML1-ETO group was significantly lower than that in the CBF?-MYH11 group(median:10.11×10E9/L vs34.8×10E9/L,P<0.001).The primary blast cells of the bone marrow in theAML1-ETO group were also significantly lower than the CBF?-MYH11 group(median:46%vs 57.5%,P<0.001).There was no significant difference in the levels of hemoglobin and platelet count between the two groups(P>0.05).Patients harbouring t(8;21)/AML1-ETO abnormality mostly subclassified as French-American-British(FAB)M2,accounting for 81.6%,followed by M4,M5,and M1 subtypes(accounting for 5.3%,8.5%and 1.1%,respectively).Patients in the inv(16)/CBF?-MYH11 group were more common observed in M4 subtype,accounting for 69.9%,followed by M5 and M2 subtypes(accounting for 19.5%,9.8%,respectively).In the AML1-ETO group,210 cases(55.4%)were expressed with lymphoid-associated antigens,15 cases(4.0%)expressed both myeloid and lymphoid-associated antigens;144 cases(56.3%)in CBF?-MYH11 group were expressed with lymphoid-associated antigens.10 patients(3.9%)expressed both antigens simultaneously.3.About karyotype analysis,127 patients(33.2%)had pure t(8;21)/inv(16)/t(16;16)abnormal rearrangement,201 patients(51.7%)had additional chromosomal abnormalities.The most common additional chromosomal abnormalities in the AML1-ETO group were sex chromosome loss-Y or-X,accounting for 47.0%(124/264)of the total,followed by del(9q)/9q-,which accounted for 8.7%.(23/264).The most common additional chromosomal abnormalities in the CBF?-MYH11 group were Trisomy,especially trisomy22,accounting for 16.8%(20/119).4.Gene mutations in the tyrosine kinase signaling pathway(TK pathway)family were most common in CBF-AML patients,mainly with receptor tyrosine kinase(RTK)related genes mutation as the rate of them were 48.5%.The rate of C-KIT mutation was high(35.4%),the rate of FLT3 mutation was relatively low(19.1%),and 8 patients were with C-KIT and FLT3 co-mutation.The mutation rate of RAS(K/NRAS)was also high,and there was a significant expression advantage in CBFp-MYH11(P=0.009).Other members of the TK pathway,including JAK2,JAK3,and CBL mutations,are relatively rare.Mutations of DNA methylation-related genes,transcription factor-related genes,and cohesin related genes could also be observed in patients who finished the second-generation sequencing.Conclusions1.Among the 416 patients with do-novo CBF-AML included in this analysis,male patients were the majority,mostly were young adult patients.2.The two cytogenetic subgroups of AML1-ETO group and CBFP-MYH11 group have similar common features as well as differences in peripheral blood,blast cells of the bone marrow ratio,bone marrow cell morphology and immunophenotype.3.More than half of CBF-AML patients were accompanied by additional chromosomal abnormalities other than t(8;21)/inv(16)/t(16;16)rearrangements.The karyotype abnormalities of the two cytogenetic subtypes also have their own characteristics.The AML1-ETO group mainly consists of sex chromosome deletion,followed by the ldel(9q)/9q-;the CBF?-MYH11 group mainly consists of trisomy,of which+22 was most common.4.The most common gene mutation in CBF-AML patients is mutations in the tyrosine kinase pathway family,in which the C-KIT mutation rate is as high as 30%,followed by N/KRAS gene mutation,FLT3 gene mutation,JAK2/3 and CBL,of which the rate is low.In addition,second-generation sequencing can find a variety of genetic mutations involving different functions.?.The analysis of the factors affecting the treatment and prognosis of prognosis and prognosis in patients with CBF-AML.Objective1.To analyze the prognosis of patients with CBF-AML and explore the related factors affecting the prognosis for early assessment and the detection of patients with poor prognosis of CBF-AML.2.To analyze the effect of allogeneic hematopoietic stem cell transplantation on the prognosis of CBF-AML,and to explore the appropriate population and timing for the choice of Allo-SCT as a method for intensive treatment.Method1?The prognosis of 379 patients who achieved complete remission after induction chemotherapy were analyzed.The influence of clinical and laboratorial characteristics including age,gender,peripheral blood cell count,proportion of BM blasts,extramedullary infiltration,cytogenetics,and gene profiling on OS and EFS of CBF-AML patients were analyzed.And to comprehensively analyze those prognostic value in combination with treatment grouping.2?According to the consolidation treatment of patients,they were divided into chemotherapy group,autologous stem cell transplantation group(Auto-SCT)and allogeneic hematopoietic stem cell transplantation group(Allo-SCT).To compared and analyze the characteristics,prognosis,OS and EFS of each group and discuss the selection of treatment strategies for patients with CBF-AML.Prognosis of the patients with different remission states within Allo-SCT group were analyzed and compared so as to discuss the influence of the timing of hematopoietic stem cell transplantation on the prognosis.ResultAmong the 379 patients who were induced to achieve first complete remission(CR1),the median follow-up time of surviving patients was 46 months(range:18-106 months).The 5-year OS rate is about 60.2%,and the 5-year EFS rate is 53.9%.Patients with age>50 years showed significant survival disadvantages in OS and EFS in the overall patient as well as the two cytogenetic subgroups(p<0.05).Gender,hyperleukocytosis,hemoglobin level,platelet count,percentage of BM blasts,extramedullary infiltration,and expression of lymphocyte antigen had no effect on OS and EFS of the two cytogenetic subgroups(p>0.05)..In the cytogenetic analysis,the t(8;21)/AML1-ETO abnormal group showed a survival disadvantage in OS and EFS compared with the inv(16)/CBF?-MYH11 group(P<0.05).The number of additional abnormal chromosomal abnormalities and additional chromosomal abnormalities(including-X/-Y,del(9q)/9q-,trisomy,etc.)did not affect the prognosis of CBF-AML(P<0.05).Molecular biological prognostic analysis showed that FLT3(FT3-ITD,FLT3-TKD)had no significant effect on OS and EFS.C-KIT mutation was a significant adverse prognostic factor(P<0.001).Combined with cytogenetic,the adverse prognosis of C-KIT mutation was more obvious in AML1-ETO group.Patients with AML1-ETO and C-KIT mutation positive had the worst OS(P<0.05),their EFS was at a distinct disadvantage compared with the C-KIT mutation negative group(P<0.05),The C-KIT mutation had no significant adverse effects on the prognosis in the CBF?-MYH11 group(P>0.05).2.379 patients who achieved CR1 after induction were divided into three groups according to the follow-up treatment:199 patients in Allo-SCT group,43 patients in Auto-SCT group,and 145 patients in chemotherapy alone group.The results showed that the OS and EFS of the chemotherapy group were the worst(P<0.05).There was no significant difference in OS and EFS between the Allo-SCT group and the Auto-SCT group(P=0.453).Prognostic analysis of treatment grouping combined with cytogenetic subgroups suggested that patients in the AML1-ETO group receiving chemotherapy alone showed the worst OS and EFS(P<0.05).In the AML1-ETO group,autologous and allogeneic hematopoietic stem cell transplantation showed no significant difference in OS and EFS.Among the patients in the CBF?-MYH11 group,the Allo-SCT group showed superior EFS compared with the chemotherapy alone group(P=0.017),and there was no statistically significant difference in OS and EFS between the other treatment groups.Prognostic analysis of the treatment groups combined with C-KIT mutation suggested that patients with C-KIT mutation positive received chemotherapy alone had the worst OS and EFS(P<0.05).Allo-SCT improved the OS and EFS in patients with C-KIT mutation positive compared with chemotherapy alone(P<0.05).Although patients with C-KIT mutation negative who received chemotherapy alone had a better prognosis than those C-KIT mutation positive patients(P<0.05),Auto-SCT and Allo-SCT were still helpful in improving their OS and EFS(P<0.05).There was no significant difference in OS and EFS between the two transplantation groups.Conclusion1.Age is an important prognostic factor for patients with CBF-AML.CBF-AML patients of age>50 years old show significant survival disadvantages.Additional karyotypic abnormalities do not affect the prognosis of the patient.The OS and EFS of AML1-ETO group were worse than those of the CBFP-MYH11 group.C-KIT mutation positive is a sign of poor prognosis.Patients with C-KIT mutation positive and AML1-ETO had the worst prognosis.2.The OS and EFS of the patients in the chemotherapy group were worse than those in the transplantation groups.The patients with AML1-ETO or C-KIT mutation positive who received chemotherapy alone showed the worst OS and EFS.Transplantation could improve the prognosis of patients with CBF-AML,and there was no significant difference in prognosis between the two transpantation groups.Prognosis analysis of patients with C-KIT mutation positive suggested that Allo-SCT could improve the prognosis of patients with C-KIT mutation positive compared with chemotherapy alone.Allo-SCT,as the choice of intensive treatment could improve the prognosis of patients with recurrence.