A Retrospective Analysis Of Clinical Characteristics And Outcomes Of Acute Lymphoblastic Leukemia Patients With TCF3-PBX1 Chimeric Gene Positive

ObjectiveTo analyze retrospectively the clinical hematological features,molecular genetic characteristics,treatment outcome and prognosis of acute lymphoblastic leukemia patients（ALL）with TCF3-PBX1（E2A-PBX1）chimeric gene in our hospital.Methods58 de novo TCF3-PBX1 positive ALL patients,including adults and children,who visited our hospital from January 1st,2011 to October 1st,2019 were collected as a subject group.While 86 fusion gene negative ALL patients（31 adults and 55 children）were randomly selected by systematic sampling as control.Since the follow-up date ended in February 1st,2020,a retrospective analysis was performed in both control and study group to collect clinical data,which including gender,age of onset,symptoms,extramedullary infiltration site,highest temperature before treatment,leukocyte,hemoglobin and platelet of initial diagnosis,percentage of immature cells,lactate dehydrogenase,bone marrow aspiration,immunophenotype,chromosome analysis,genetic testing,therapeutic regimen,remission time,time and frequency of relapses,transplantation and long term survival.Followed by evaluating the therapeutic effect and prognosis according to the complete remission（CR）rate,recurrence rate,relapsed-free survival（RFS）rate,and overall survival（OS）rate comparing by SPSS25.0 software.Results1.58 TCF3-PBX1 fusion gene positive ALL were diagnosed from 1917 de novo ALL patients,and the positive rate was 3.03%,in which adults and pediatric accounted for 2.10%（18/858）and 3.78%（40/1059）respectively.After comparing with control group（86 fusion gene negative ALL patients）,the 58 TCF3-PBX1 chimeric gene positive patients showed significant differences in the main symptoms,the site of extramedullary infiltration,leukocyte,hemoglobin of initial diagnosis,the percentage of immature cells and the lactate dehydrogenase.2.40%cases（14/35）with immunophenotype Pre-B-ALL were detected characterizing with CD10⁺/CD19⁺/CD22⁺/CD34^-/CD20^+/-special antigen co-expression pattern,while 60%（21/35）cases were common B-ALL.31.8%（14/44）patients（13children and 1 adult）were chromosomal translocation t（1;19）positive,in which 3 with balanced t（1;19）and 11 with unbalanced der（19）t（1;19）.In those 14 t（1;19）positive patients,5 cases were accompanied by other chromosome structure abnormalities and 3cases with number abnormalities.3.The total CR rate of adult patients in study and control group was 88.2%（15/17）and 96.8%（30/31）respectively,with the recurrence rates after CR was 46.7%（7/15）and 56.7%（17/30）,which showed no statistical significance（P>0.05）.The median recurrence time in study group was 4（1-20）months,while 11（4-54）months in control group.In children,the total CR rate in both TCF3-PBX1 positive and negative group with medium risk were 100%,while the recurrence rate was 15.6%（5/32）and 1.8%（1/55）which indicated a significant difference（P<0.05）.4.By the follow-up date of 2020.02.01,5 cases（29.4%）in the adult with TCF3-PBX1 positive group still survived while 12 cases（70.6%）died.The 1-year,2-year and 3-year RFS were 58.7%,34.2%and 25.7%,with the 1-year,2-year and3-year OS were 50.2%,29.3%and 22.0%respectively.In the control group,10 cases（32.3%）survived and 21 cases（67.7%）died,with the 1-year,2-year and 3-year RFS were 59.4%,37.8%and 30.3%and the 1-year,2-year and 3-year OS were 73.9%,57.1%and 38.7%respectively.These results indicated there was no statistically significant difference in RFS and OS between two groups（P>0.05）.In adults study group,the 1-year,2-year and 3-year RFS of patients with or without transplantation showed 100%vs 42.4%,50%vs 28.3%,50%vs 14.1%,the 1-year,2-year and 3-year OS were 100%vs 33.6%,50%vs 22.4%,50%vs 11.2%respectively,which also showed no statistical difference between the two groups（P>0.05）.Unlike in adults,instead,27 cases（84.3%）of survival and only 5 cases（15.6%）of death in the children study group were observed,with the 1-year,2-year and 3-year RFS were 90.5%,86.7%and 81.6%and the 1-year,2-year and 3-year OS were 96.9%,93.5%and 89.8%respectively.Compared with study group,all patients in the control group were survived.The 1-year,2-year and 3-year RFS were 98.1%,98.1%and 98.1%,with the1-year,2-year and 3-year OS were 100%,100%and 100%respectively.These results showed a strong statistical difference in RFS and OS between study and control groups（P<0.05）.Conclusion1.TCF3-PBX1 chimeric gene positive ALL is a unique subtype of ALL,with highly heterogeneous.The onset was mostly accompanied with high leukocyte count,the percentage of immature cells,lactate dehydrogenase level and extramedullary infiltration site.2.The Pre-B-ALL phenotype in TCF3-PBX1 positive ALL showed a special antigen co-expression pattern of CD10⁺/CD19⁺/CD22⁺/CD34^-/CD20^+/-.TCF3-PBX1fusion genes characterized by chromosomal translocation t（1;19）,in which unbalanced translocation was common and karyotypes may accompany by other chromosomal abnormalities.3.Compared with control group,the TCF3-PBX1 positive pediatric patients showed a short-term recurrence after remission,shorter RFS and OS.The allogeneic hematopoietic stem cell transplantation could improve the prognosis of such patients.