| Background and ObjectiveAcute leukemia(AL)is a common malignant disease of hematopoietic tissues.Epidemiological surveys show that the incidence of leukemia is about 3 to 4 per100,000 and is one of the top 10 most prevalent neoplasms that seriously endanger human health.Acute myeloid leukemia(AML)is the most common type of acute leukemia in adults,with rapid onset,severe disease,rapid progression and low survival rate.The pathogenesis of AML is based on impaired maturation,excessive proliferation and impaired apoptosis of hematopoietic stem cells during differentiation caused by genetic mutations.Currently,the ELN risk stratification system based on the molecular genetics and cytogenetics of AML has promoted the development of precise treatment of leukemia;however,the combination of relevant molecular alterations and the traditional stratification system is still in an imperfect state,and there is still room for optimization.More prognostic factors impacting AML need to be further explored.Cytomorphology not only provides an important basis in the diagnosis and type of AML,but also its relationship with molecular genetics,cytogenetics,Immunophenotyping and prognosis has been increasingly explored.Vacuolated blasts are often observed in bone marrow morphology smears of initial AML patients.However,their clinical significance has not been fully clarified.Recently,it has been found that AML patients with blast vacuolization have a relatively short overall survival.In this study,we observed the features of vacuolated blast in patients with initial AML under a light microscope,collected clinical data from these patients,and followed up regularly to investigate the correlation of vacuolated blast in bone marrow with genetic alterations and prognosis in acute myeloid leukemia.MethodsThe clinical data of 152 patients with initial AML(non-acute promyelocytic leukemia,APL)attending an*affiliated hospital of Zhengzhou University between January 2015 and December 2019 were collected,and all patients were perfected with blood routine,blood biochemistry,immunophenotyping,bone marrow morphological analysis,histochemical staining,cytogenetic and molecular genetics.According to the description of calculating the percentage of vacuolated blasts and the grouping criteria in the study of Olivier et al[1],under a light microscope,Wright-Giemsa-stained BM aspirate smears were observed and the vacuolated blasts were counted under a microscope,and the percentage of blasts with vacuoles/100 blasts was calculated and categorized.A cut-off of 10%was used to divide 152 patients with AML(non-APL)into a high percentage of vacuolated blast group(>10%)(H-v AML)and a low percentage of vacuolated blast group(≤10%)(L-v AML).We also explored the correlation of vacuolated blast in bone marrow with clinical characteristics of disease(age,gender,FAB type,lactate dehydrogenase,percentage of bone marrow blast cells,percentage of peripheral blood blast cells,immunophenotype,cytogenetics,molecular biology)and treatment outcome(complete remission rate,partial remission rate,non-remission rate after 1 course of chemotherapy)and survival time.Results1.Clinical features:Among 152 patients with AML(non-APL),47(30.9%)were in the H-v AML group and 105(69.1%)were in the L-v AML group.No statistical differences were found between the two groups in age of onset,gender,white blood cell count,hemoglobin,platelet count,and bone marrow/peripheral blood blast cell percentage(P>0.05).2.genetic alterations:according to the risk stratification established by the 2017ELN’s AML treatment guidelines,most of the patients in high-risk group had high percentage of vacuolated blasts(χ~2=17.389,P<0.001),while low percentage of vacuolated blasts was associated with the low-risk group(χ~2=5.768,P=0.016).Further analysis of molecular genetics and cytogenetic features showed that the rate of TP53mutations,IDH1/IDH2 mutation and karyotype complex were higher in the H-v AML group than L-v AML group,a difference that was statistically significant(all P values<0.05).3.a high-percentage of vacuolated blasts was more likely to be associated with a higher expression of CD71 than a low-percentage vacuolated blasts(P=0.006),and no significant difference was detected in the expression of other immunophenotypes among the three groups(P>0.05).4.Therapeutic outcome analysis:After 1 course of induction chemotherapy,the complete remission rate(CR)of AML patients in the H-v AML group was significantly lower than that in the L-v AML group,and the difference was statistically significant(29.8%vs 64.8%,χ~2=15.985,P<0.001);the partial remission rate(PR)and non-remission rate(NR)of AML patients in the H-v AML group were higher than those in the L-v AML group,and the differences were statistically significant(46.8%vs 29.5%,χ~2=4.271,P=0.03;23.4%vs 5.7%,χ~2=10.228,P=0.001).5.Prognostic analysis.5.1.Among all AML(non-APL)patients,the 1-year overall survival(OS)rate and event-free survival(EFS)rate of AML patients in the H-v AML group were significantly lower than those in the L-v AML group(34%vs 64%and 25%vs 58%),and the difference was statistically significant(both P values<0.05.)Blast vacuoles is an independent prognostic factor for both OS and EFS.5.2.Prognostic analysis for age stratification:For AML aged>60 years,patients with AML in the H-v AML group had lower OS and EFS than those in the L-v AML group(1-year OS rate:21%vs 53%,P=0.008;1-year EFS rate:10%vs.45%,P=0.001).Among AML patients aged 60 years,patients with AML in the H-v AML group also had lower OS and EFS than those in the L-v AML group(1-year OS rate:43%vs 66%,P=0.038;1-year EFS rate:34%vs 61%,P=0.009).5.3.Prognostic analysis for ELN risk stratification:among AML patients in the ELN-high risk group,there was no statistical difference on OS and EFS between AML patients in the H-v AML group and the L-v AML group(both P values>0.05);among AML patients in the ELN-intermediate risk group,there was still no statistical difference between the two groups(both P values>0.05);however,among AML patients in the ELN-low risk group,t AML patients in the H-v AML group had lower OS and EFS than the L-v AML group(1-year OS rate:31%vs 62%,P=0.017;1-year EFS rate:19%vs 61%,P=0.001).5.4.Among patients with normal karyotype AML,patients with AML in the H-v AML group had lower OS and EFS than those in the L-v AML group(1-year OS rate:31%vs 66%,P=0.007;1-year EFS rate:26%vs 58%,P=0.002).Conclusion1.In AML(non-APL)patients,high percentage of vacuolated blasts are associated with specific genetic mutations(TP53,IDH1/2)and complex karyotypes.2.CD71,an indicator of tumor cell proliferation,was highly expressed in AML patients in the H-v AML group.3.Blast vacuolation is an independent prognostic factor for both OS and EFS in AML patients,and AML patients in the H-v AML group have lower complete remission rate and short survival time.Cytoplasmic vacuoles may serve as a simple and effective marker to assess the therapeutic outcome and prognosis of AML.4.In AML patients with aged>60 and 60 years,ELN-low risk group and normal karyotype AML,AML patients in the H-v AML group had relatively poor OS and EFS.Among patients with initial AML,blast vacuoles,a morphological feature of poor prognosis,provide a useful complement to the classical ELN risk stratification of AML... |
