Banca de DEFESA: Estefânia Rodrigues Biojone

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Estefânia Rodrigues Biojone
DATE: 19/11/2024
TIME: 08:30
LOCAL: Hospital da Criança de Brasília - CISEP Sala 01
TITLE:

Epidemiological Profile and Molecular Characterization of Pediatric B-cell Acute Lymphoblastic Leukemia and its Impact on Clinical Outcomes of Patients Treated at a Brazilian Tertiary Public Hospital

KEY WORDS:

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precision Medicine; Molecular Biology; Tumor Biomarkers

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

INTRODUCTION: Acute Lymphoblastic Leukemia (ALL) is the most common cancer in childhood, accounting for 30% of pediatric neoplasms. The peak incidence occurs between 2 and 5 years of age, with survival rates exceeding 90% in developed countries. In developing countries, survival rates are lower, attributed to limited access to healthcare and higher mortality from treatment-related toxicity. Even under optimal conditions, certain subgroups of B-ALL patients do not respond to treatment or experience relapse. Biological characterization has enabled the identification of new B-ALL subtypes and the development of novel therapeutic tools. In Brazil, leukemia assessment through molecular biology and genetic sequencing is restricted to a few research centers. Thus, there is a need to determine the biological subtypes of B-ALL and their clinical course at a Brazilian reference center. OBJECTIVES: To identify the biological subtypes of B-ALL, describe the frequency of these subtypes, and correlate them with clinical outcomes. METHODOLOGY: Patients aged 1 to 18 years, admitted to the HCB with a diagnosis of B-ALL between July 2018 and September 2023, were evaluated. Patients received treatment according to two protocols: modified BFM-ALLIC2009 (122 patients) and GBTLI2021 (34 patients). For biological characterization, bone marrow samples were evaluated by conventional cytogenetics, RT-PCR (ETV6::RUNX1, TCF3::PBX1, BCR::ABL1, rKMT2A, P2RY8::CRLF2), MLPA (IKZF1, PAX5, ERG, iAmp21), RFLP, capillary fragment analysis (FLT3 mutations), and Next-Generation Sequencing (NGS). The correlation between B-ALL biological subtypes and minimal residual disease (MRD) values, relapse occurrence, overall survival (OS), and event-free survival (EFS) rates was analyzed. RESULTS: A total of 156 patients were evaluated. OS rates were 100%, 86%, and 59% in patients treated with the adapted BFM-ALLIC2009 protocol and classified as low, intermediate, and high risk, respectively. The leading cause of death was infection associated with neutropenia. Fourteen B ALL subtypes were identified, encompassing 86% of patients. ETV6::RUNX1 ALL (26%) and high hyperdiploidy (19%) were the most common subtypes. Patients with IKZF1plus had lower OS (48%, p=0.04, Log-rank Mantel Cox Test), PAX5 alterations were associated with higher MRD levels on D33 (p=0.03, Mann-Whitney Test), higher relapse risk (Fisher's Exact Test, p=0.04), and lower survival (OS 33%, p=0.005, EFS 55.5%, p=0.01). FLT3 TKD mutation was associated with relapse (Fisher's Exact Test, p=0.04). Patients with P2RY8::CRLF2 did not show unfavorable outcomes. CONCLUSION: Survival rates are below those observed in international centers and could be improved by reducing treatment-related mortality. The divergent clinical outcomes in certain B-ALL subtypes underscore the importance of characterizing the biology and progression of B-ALL in Brazil. We identified the need to increase sample size and assess new markers, including genetic factors associated with greater susceptibility to chemotherapyrelated toxicity, which may explain the higher treatment-related mortality.

COMMITTEE MEMBERS:
Externo à Instituição - JOSÉ ANDRÉS YUNES
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