Clinical Analysis Of The Relapse Of Childhood Acute Lymphoblastic Leukemia

Objective:To study the risk factors of relapse for pediatric acute lymphoblastic leukemia(ALL),and clinical characteristics and prognosis of relapsed ALL under current treatment protocols.Method:The clinical data of 755 children with newly diagnosed ALL from April 2008 to December 2016 in the Children’s Hospital of Chongqing Medical University were retrospectively collected.The cumulative incidence of relapse(CIR)of B-ALL under various clinical features were analyzed and multivariate regression analysis was performed.The CIR of T-ALL was analyzed separately.And the data of 155 relapsed ALL between April 2008and December 2018 were analyzed to explore the clinical features and prognosis of relapsed ALL.Result:Up to December 2019,143 of the 755 newly diagnosed patients relapsed,with a 5-year CIR of 20.5%.Analysis of relapse risk factors for B-ALL:patients with characteristics like age≥10 years,WBC≥100×10~9/L,BCR-ABL1,MLLr,positive D33(46)bone marrow MRD showed higher CIR;age≥10 years,WBC≥100×10~9/L and positive D33(46)MRD were the independent risk factors of relapse in B-ALL;features like gender,WBC(50-99.9)×10~9/L,CNS status,high hyperdiploidy,ETV6-RUNX1,TCF3-PBX1were not significantly related to relapse.The 3-year CIR of T-ALL in CCLG-ALL2008 protocol was 34.1%and higher than B-ALL(10-year CIR,34.1%vs 21.1%,P=0.011),the 3-year CIR of T-ALL in CCCG-ALL-2015 protocol was not significantly elevated compared to B-ALL(20.0%vs 13.4%,P=0.747).Of the 155 relapsed ALL,the percentage of very early,early and late relapse was 50%,27%and 23%,respectively.There were 67 isolated bone marrow relapses,15 combined bone marrow relapses and 40 isolated extramedullary relapses in the 122 patients with thorough assessment of relapse sites.After relapse,67 patients were treated and 76%achieved remission,with a 2-year event-free survival and overall survival of51.6%±6.7%and 64.0%±6.4%.Patients with bone marrow relapse,T-ALL,BCR-ABL1 or MLLr,age≥10 years had worse prognosis after relapse.Conclusion:Age≥10 years,WBC≥100×10~9/L and positive end-of-induction MRD were the independent relapse risk factors of pediatric B-ALL.The CIR of T-ALL in CCLG-ALL2008 protocol was significantly higher than B-ALL,and in CCCG-ALL-2015 protocol,T-ALL was not significantly related to relapse and showed lower CIR.The difference of relapse risk factors between the two protocols indicated that relapse risk factors could change with treatment protocols,meanwhile providing clues for adjusting treatment.More efforts are needed for exploring potential relapse risk factors,optimizing risk stratification and reducing relapse rate.The prognosis of patients with bone marrow relapse,T-ALL,BCR-ABL1 or MLLr,age≥10 years was worse after relapse.Improvement of chemotherapy protocols and development of novel approaches are needed to increase survival of relapsed ALL.