Quantification of minimal residual disease in acute lymphoblastic leukemia by high throughput sequencing

• Grant number: 17/03942-8
• Support type: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2018
• Effective date (End): February 28, 2019
• Field of knowledge: Health Sciences - Medicine
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: José Andrés Yunes
• Grantee: Guilherme Navarro Nilo Giusti
• Home Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. The current childhood ALL treatment protocols achieve disease-free survival rates higher than 70%. Part of this success is due to the allocation of patients in different risk groups, according to pre-treatment prognostic factors. Initial treatment response, assessed by the quantification of residual leukemic cells, or Minimal Residual Disease (MRD), is one of the most important factors to identify these risk groups. The current protocol of the Brazilian Group for the treatment of ALL (GBTLI LLA-2009) uses DRM at days 15 and 35, evaluated by flow cytometry and RQ-PCR, to allocate the patients into groups for different chemotherapy treatment schemes. Flow cytometry and RQ-PCR DRM assessment is an expensive method, requires a lot of experience from the analyst and demands an immediate analysis (cytometry) or a multistep 25.days-long analysis (RQ-PCR). These factors hamper these methods' broad utilization in Brazil. The number of children in the country who are able to take advantage of the DRM exam is 100 a year (3,5% of total ALL in our country). In this Project, we intend to standardize DRM assessment in childhood ALL by Next Generation Sequencing of IgH rearrangements. This assay is cheaper than the conventional ones, fast and has high scalability potential. Once standardized, this method will be validated using previously analyzed samples from Centro Boldrini. The results will be compared with the ones achieved by RQ-PCR DRM. We hope to establish a universally applicable method for DRM assessment in childhood ALL in Brazil. (AU)