| Background:Acute lymphoblastic leukemia(ALL)is the most common hematological tumor in children and adolescents.It’s prognostic factors mainly include age,white blood cell count at initial diagnosis,cytogenetics,molecular biology and other clinical and biological characteristics,as well as treatment response,which is represented by minimal residual disease(MRD).The E2A-PBX1(TCF3-PBX1)fusion gene is formed by t(1;19)(q23;p13)resulting in the fusion of PBX1 gene on chromosome 1 with E2A gene on chromosome 19,which was first described by Carroll in 1983.It is an important recurrent genetic abnormality in acute lymphocytic leukemia,accounting for about 6%of childhood ALL and 3%of adult ALL.Previous studies had shown that E2A-PBX1-positive ALL was characterized by high white blood cells counting at initial diagnosis,high lactate dehydrogenase,high central nervous system leukemia rate and poor outcome.With the continuous optimization of childhood ALL treatment,the overall survival rate of children with E2A-PBX1-positive ALL is significantly improved,and the current risk stratification is classified into the intermediate risk group;However due to its low incidence,there is few report about the clinical features,treatment response and prognosis of adult E2A-PBX1-positive ALL.Objective:To analyze the clinical features,treatment responses and outcomes of adult patients with E2A-PBX1 fusion gene.Methods:The clinical data of 91 Philadelphia-negative BCP-ALL patients(age≥14 years old)who were admitted to the Department of Hematology,from March 2015 to December 2017 were collected.According to the fusion gene,at first they were divided into E2A-PBX1-positive group and E2A-PBX1-negative group to analyze.And then they were further divided into E2A-PBX1-positive group,MLL-AF4-positive group,and other ALL group three groups for subgroup analysis.The clinical features,responses and prognosis of the E2A-PBX1-positive ALL were retrospectively analyzed by comparing between groups.Results:(1)The E2A-PBX1 fusion gene was detected in 11 patients from March 2015 to December 2017.Of these,the average age was 27.2 years old(range 14 to 45 years old),the average of newly diagnosed white blood cell(WBC)count was 32.96×109/L(range 6.18×109/L to 91.57×109/L),the mean lactate dehydrogenase(LDH)was 3880.6(range 1070 to 9554)U/L;At the same time,there were 80 cases of E2A-PBX1-negative ALL.The average age was 28.5 years old(range 14 to 59 years old),the average of WBC was 35.39×109/L(range 0.60×109/L to 408.12×109/L),the mean lactate dehydrogenase was 1110.1(range 103 to 18651)U/L.There was no statistical significant difference except LDH(P=0.003)between the E2A-PBX1-positive ALL and E2A-PBX1-negative ALL,such as gender,age,WBC and extramedullary invasion rate.(P>0.05).(2)The immunophenotypes of 11 E2A-PBX1-positive ALL patients were common-B cell phenotype.4 patients showed the expression of CRLF2、phosphorylated CRKL、phosphorylated STAT5 by using flow cytometry,which were similar to Philadelphia-Like ALL.(3)On treatment response,the E2A-PBX1-positive ALL group had a good reaction in the end of first course induction chemotherapy.The complete remission(CR)rate and minimal residual disease(MRD)-negative rate for E2A-PBX1 positive-ALL group were 81.8%and 63.6%respectively after 1 course of induction chemotherapy.But the recurrence rate was 80.0%.4 patients accepted hematopoietic stem cell transplantation.In E2A-PBX1 negative ALL group,The CR rate and MRD-negative rate for E2A-PBX1were 88.8%and 66.3%respectively after 1 course of induction chemotherapy.The recurrence rate was 34.2%,43 patients received hematopoietic stem cell transplantation;Significant differences were not found whether in the CR rate or in MRD negative rate after induction between the two groups(P=0.617、0.864).but the recurrence rate of the E2A-PBX1-positive group was significantly higher than the negative group(P=0.012).(4)The median follow up time was 17 months,and the 1-year overall survival(OS)rate and event-free survival(EFS)rate of E2A-PBX1-positive ALL group were 43.6%、13.6%respectively,which were significantly lower than the negative group(70.0%,60.0%,P=0.020、0.002).Surprisingly subgroup analysis showed no statistical difference between E2A-PBX1-positive ALL group and MLL gene rearrangement ALLgroup in EFS and OS(P=0.989、0.617).Conclusions:The E2A-PBX1-positive ALL make up a small proportion of adult ALL and there is no significant difference in clinical biological characteristics comparing with other subtypes.On treatment response,it is characterized by high complete remission rate and high cumulative recurrence rate which is similar to the ALL with MLL gene rearrangement.It is a high risk genetic abnormality and its risk stratification should be classified into the high-risk group.E2A-PBX1-positive ALL may share the same mutations in some essential signaling pathways with Philadelphia-like ALL and need to explore further immunotherapy and targeted therapy strategies. |
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