Relative Telomeric Length of Bone Marrow Cells at Diagnosis and Its Association with Minimal Residual Disease in Juvenile Acute Lymphoblastic Leukemia

Abstract

Introduction: Identification of prognostic factors at diagnosis, risk stratification and the analysis of minimal residual disease (MRD) may predict treatment outcomes for children diagnosed with Acute Lymphoblastic Leukemia (ALL). A possible prognostic indicator is bone marrow mononuclear cells telomeric length at diagnosis. Currently, the best predictor of treatment response and disease-free survival is the analysis of MRD. Objectives: To investigate the association between bone marrow mononuclear cells telomeric length in children and adolescents with ALL at the time of diagnosis and the assessment of MRD on days 15, 33 and 78 after initiation of treatment. Methods: This study included patients aged 1 to 18 years, diagnosed with ALL and treated at Hospital da Criança de Brasília José Alencar. The telomeric length was determined by real-time polymerase chain reaction (qPCR) from a sample of bone marrow aspirate collected at the diagnosis. MRD was performed by flow cytometry immunophenotyping on days 15, 33, and 78 of chemotherapy. Risk stratification was determined according to specifications from BFM 2009 protocol. Results: 79 subjects were included in the study. Patients with negative MRD on D33 had significantly longer telomeric length (p = 0.02) when compared with those with positive MRD on D33. Patients classified as high risk had a higher frequency of positive MRD on D33 (p<0.01). Only positive DRM on D33 was a predictor of shorter telomeric length at diagnosis. Telomeric length at diagnosis was not related to D15 or D78 MRD results. Conclusion: This study suggests that longer telomeric length may be associated with a better prognosis, since these patients have negative MRD on D33. This result demonstrates that the assessment of the telomeric length of bone marrow cells from pediatric patients with ALL at the time of diagnosis can be a potential prognostic factor.