Correlation Of Telomere Length With Clinical Characteristics And Treatment Outcome Of Pediatric Acquired Aplastic Anemia

Objective To reveal telomere length distribution in children with aplastic anemia.To explore the association between the clinical characteristics and telomere length in pediatric patients with acquired aplastic anemia(AA).To assess the relationship between telomere length and treatment outcome of pediatric patients with non-severe aplastic anemia(NSAA)and severe aplastic anemia(SAA)separately.And to explore the distribution of chromosome karyotype、hematologic tumor-related mutations and telomere-related mutations in patients with aplastic anemia and their relationship with telomere length:Methods The mean telomere length of patients was measured using terminal restriction fragment(TRF)and adjusted with patient age.We reviewed 128 pediatric patients with acquired aplastic anemia in our center to analyze the correlation between clinical characteristics and age-adjusted telomere length(Z).The age-adjusted telomere length differences were compared between patients with and without abnormal chromosome karyotype,hematologic tumor-related mutations and inherited bone marrow failure related mutations,and we described the treatment and prognosis of patients with telomere-related mutations.The relationship between age-adjusted telomere length and response to drug therapy was retrospectively analyzed using univariate Logistic regression.And we described the age-adjusted telomere length and the treatment response in patients treated with ATG and transplantation.Results 128 eligible children with acquired aplastic anemia were enrolled in this study,including 76 patients with nonsevere aplastic anemia and 52 patients with severe aplastic anemia.The mean age-adjusted telomere length for NSAA patients was-1.84±1.19,which significantly lower than the mean age-adjusted telomere length for SAA patients of-1.44±0.97(p=0.044).Using multivariate logistic regression,progression was found to be related with short telomeres in NSAA patients(OR=5.787,95%CI 1.459-32.439,P=0.0224),whereas no other clinical features were found to be related with age-adjusted telomere length in SAA patients,the abnormal chromosome karyotype rate was 4.1%.The telomere length of NSAA patients with abnormal chromosome karyotype was shorter than that of NSAA patients with normal chromosome karyotype,but the results were not significant(P=0.5219).A total of 120 patients with hematologic tumor-associated gene sequencing were enrolled in the study,and the hematologic tumor-associated gene mutation rate was 15.8%.The telomere length of NSAA patients with hematologic tumor-associated mutations was shorter than that of NSAA patients without mutations,but the results were not significant(P=0.2223).The telomere length of SAA patients with hematologic tumor-associated mutations was also shorter than that of SAA patients without mutations,but the results were not significant(P=0.3059).A total of 90 AA patients in the enrolled group completed inherited bone marrow failure disorders genetic testing,in which the telomere related gene mutation carriage rate was 7.8%.The telomere length of NSAA patients with telomere related mutations was shorter than that of NSAA patients without mutations,but the results were not significant(P=0.7376).The telomere length of SAA patients with telomere related mutations was shorter than that of SAA patients without mutations,but the results were not significant(P=0.3732).49 of 76 NSAA patients were treated with drug therapy.Grouped by the upper quartile of age-adjusted telomere length(-0.88)in AA patients,the response rate to drug therapy was lower in patients with short telomeres(40.50%)than in patients with long telomeres(60.00%).However,univariate Logistic regression showed no significant association between telomere length and response to drug therapy in NSAA patients(P=0.278).15 out of 52 patients with SAA were treated with drug therapy,and univariate Logistic regression showed no significant association between telomere length and response to drug therapy in patients with SAA(P=0.996).Conclusion The age-adjusted telomere length was significantly lower in patients with non-severe pediatric aplastic anemia than in patients with severe pediatric aplastic anemia.Progression correlated with age-adjusted telomere length in non-severe aplastic anemia patients.The carriage rate of abnormal chromosome karyotype in pediatric aplastic anemia patients was 4.1%,the carriage rate of hematologic tumor-associated gene mutations in pediatric aplastic anemia patients was 15.8%.and the carriage rate of telomere-associated gene mutations in pediatric aplastic anemia patients was 7.8%.The telomere length of AA patients with abnormal chromosome karyotype was shorter than that of AA patients with normal chromosome karyotype.but the difference was not significant.The telomere length of AA patients with telomere-associated gene mutations was shorter than that of AA patients without telomere-associated gene mutations,but the difference was not significant.The response rate to drug therapy was lower in non-severe aplastic anemia patients with shorter age-adjusted telomere length than in patients with longer age-adjusted telomere group,but short telomeres were not an independent factor to drug therapy response in patients with non-severe aplastic anemia.And telomere length was not significantly associated with response to drug therapy in patients with severe aplastic anemia.