Banca de QUALIFICAÇÃO: Estefânia Rodrigues Biojone

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : Estefânia Rodrigues Biojone
DATE: 29/04/2024
TIME: 14:00
LOCAL: Plataforma Virtual - Microsoft Teams
TITLE:

Characterization of B Acute Lymphoblastic Leukemia in children regarding biological subtypes and correlation of ALL subtypes with clinical evolution

KEY WORDS:

Acute Lymphoblastic Leukemia; ALL Ph like; Minimal residual disease; ALL Biological Markers; Childhood Leukemia

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

INTRODUCTION: Survival in Acute Lymphoid Leukemia (ALL) exceeds 90% in developed countries. In low resources countries, survival rates are lower, which is attributed to limited access to diagnosis and treatment and higher mortality due to toxicity. Even under ideal care conditions, there are subgroups of patients with B-ALL who do not respond to treatment or relapse. The genetic and molecular characterization of leukemic cells provided a better understanding of the mechanisms associated with the genesis of B-ALL and the identification of new subtypes of B-ALL, opening the possibility for the development of new therapeutic tools. In Brazil, the characterization of leukemia using molecular biology and genetic sequencing methodologies is still restricted to a few research centers. In this context, there is a need to determine the prevalent subtypes and their biological behavior in Brazilian patients. OBJECTIVES: Identification of biological subtypes of B-ALL in children and adolescents in Brazil, description of the frequency of different subtypes and correlation of biological subtypes with treatment response rates and clinical evolution. METHODOLOGY: Were evaluated 148 children aged between 1 and 18 years, admitted to the Pediatric Oncology service of Hospital da Criança de Brasília with a diagnosis of B-ALL from July 2018 to August 2023. Patients received treatment according to two different protocols: modified ALL IC BFM 2009 (122 patients) and GBTLI 2021 (26 patients). To characterize the biological subtype, cytogenetic, RT-PCR, in situ hybridization (FISH), MLPA (Multiplex Ligation-dependent Amplification) and Next Generation Sequencing (NGS) tests were performed (in progress). The correlation between the different biological subtypes of ALL and clinical evolution was studied, assessed through Minimal Residual Disease (MRD) during and at the end of induction, occurrence of relapse and overall survival (OS) and event-free survival (EFS) rates. RESULTS: The 5-year OS and EFS rates were 85.7% and 78.2% respectively. Among patients treated by the BFM protocol, overall survival rates were equal to 100%, 85% and 66% for low, intermediate and high risk. Infections related to treatment toxicity were the main cause of death, especially during the second induction phase. ETV6/RUNX1 ALL was the most common biological subtype, followed by high hyperdiploidy. Changes in IKZF1 were correlated with high MRD values at different times and with lower survival rates. The presence of TCF3/PBX1 and iAmp21 were not related to unfavorable outcome. CONCLUSION: OS and EFS rates were satisfactory but can be increased by reducing mortality associated with treatment. The greater frequency of some alterations (such as hypodiploidy) and an apparent divergent evolution from that described in some B-ALL subtypes (iAmp21 and TCF3/PBX1) reinforce the importance of understanding the biological behavior of B-ALL in Brazil. It is necessary to carry out studies with a larger number of patients and evaluate factors that may be associated with greater susceptibility to the toxic effects of chemotherapy.

COMMITTEE MEMBERS:
Externo à Instituição - CARLOS ALBERTOS SCRIDELI - USP
Presidente - 1764941 - DIEGO MADUREIRA DE OLIVEIRA
Externo ao Programa - 1912768 - FELIPE SALDANHA DE ARAUJO - nullExterno ao Programa - 2001303 - RODRIGO HADDAD - null