The Clinical-biological Characteristics And Prognosis Of Childhood Acute Lymphoblastic Leukemia With CDKN2A Gene Deletion

OBJECTIVE:To discuss the clinical-biological characteristics and prognosis of childhood acute lymphoblastic leukemia with CDKN2A Deletion.METHODS:A total of newly diagnosed 534 childhood acute lymphoblastic leukemia were identified retrospectively from September 2016 to April 2019 at.Institute of Hematology and Blood Diseases Hospital.All patients treated by CCCG-ALL 2015 protocol.We compared the clinical characteristics at diagnosis,immunophenotype,risk stratification,cytogenetic abnormality,early treatment response and prognosis of the CDKN2A-deleted group and the CDKN2A-wild group.We also analyzed the prognost ic factors in the CDKN2A-deleted patients.SPSS 23.0 statistical software was used for statistical analysis.RESULT:Of 534 cases enrolled,86(16.1%)patients with CDKN2A deletion.There was si gnificant difference between CDKN2A-deleted group and CDKN2A-wild group for WBC counts at presentation(29.8 vs 9.6×109/L),hemoglobin content(85.5 vs 80.0g/L),hepatosplenomegaly(64.0%vs 43.8%),T i mmunophenot ype(22.1%vs 6.5%),risk stratification[higher intermediate-risk groups(61.6%vs 49.3%,P=0.037)and lower low-risk groups(36.0%vs 48.9%,P=0.029)],hypodiploid(8.1%vs 2.9%),pseudodiploid(7.0%vs 1.1%),WT1 high expression(31.4%vs 17.6%)and TEL-AML1 fusion gene(12.8%vs 25.2%)(P<0.05).We also investigated the difference in early treatment response between two groups.CDKN2A-deleted group had significantly higher frequency of PPR than CDKN2A wild group(68.9%vs 53.5%,P<0.01)and lower frequency of MRD positive on day 19(53.5%vs 68.9%,P<0.01).Multivariable analysis suggested that both PPR(HR=3.122,95%CI 1.045-9.328)and MRD≥0.01%at day 46(HR=5.179,95%CI 1.779-15.078)were independent prognostic factor for event free survival(P<0.05).The follow up time was 21(1-40)months.CDKN2A-deleted patients had significant inferior outcomes including decreased 3 years event free-survival(EFS)(65.1±8.5%vs 85.8±3.0%),3 years relapse free-survival(RFS)(67.2±8.0%vs 87.5±3.0%)(P<0.05).CDKN2A-deleted B-ALL patients had significant inferior outcomes including decreased 3 years EFS(65.1±8.5%vs 85.8±3.0%),3 years RFS(67.2±8.0%vs 87.5±3.0%)(P<0.05).CONCLUSION:CDKN2A-dele ted ALL children have higher WBC counts,hepatosplenomegaly,higher intermediate-risk groups in risk stratification at diagnosis.T-ALL is more prevalent in CDKN2A-deleted ALL children.CDKN2A-deleted group also have quite difference in cytogenetic and genetic abnormalities,including higher percentage in complex karyotype,hypodiploid,pseudodiploid,WT1 high expression,BCL-ABL1 fusion gene and lower proportion of TEL-AML1 fusion gene.CDKN2A-deleted group have significantly higher PPR proportion.Both PPR and MRD positive at day 46 are independent prognostic factor for event free survival.CDKN2A-deleted patients had inferior EFS rate and RFS rate in CDKN2A-deleted B-ALL patients.