{"id":31306,"date":"2024-08-11T12:45:54","date_gmt":"2024-08-11T10:45:54","guid":{"rendered":"https:\/\/imagineformargo.org\/?p=31306"},"modified":"2024-08-11T12:45:54","modified_gmt":"2024-08-11T10:45:54","slug":"evaluation-of-residual-disease-by-next-generation-sequencing-ngs-in-childhood-aml","status":"publish","type":"post","link":"https:\/\/imagineformargo.org\/en\/evaluation-of-residual-disease-by-next-generation-sequencing-ngs-in-childhood-aml\/","title":{"rendered":"Evaluation of Residual Disease by Next-Generation Sequencing (NGS) in Childhood AML"},"content":{"rendered":"

\"Leuc\u00e9mies\"<\/h2>\n

Acute Myeloid Leukemias in Children<\/strong><\/h2>\n

Acute myeloid leukemia<\/a> (AML)<\/strong> is a cancer of the blood and bone marrow. AML is the second most common leukemia in children, after acute lymphoblastic leukemia (ALL). Each year, approximately 80 children in France are diagnosed with AML. It is most frequent during the first two years of life and adolescence.<\/p>\n

Although more than 90% of children achieve complete remission, the relapse rate in the first complete remission remains high (40-50%), despite advances in understanding tumor mechanisms, risk group stratification, and improvements in intensive chemotherapy and bone marrow transplantation. The overall risk of relapse remains the most common cause of death.<\/p>\n

About the Project<\/strong><\/h2>\n

The rapid identification of patients at higher risk of relapse after initial treatment is essential to quickly offer these patients more intensive treatment and improve their chances of recovery.<\/p>\n

Measuring the level of disease persistence after chemotherapy (called residual disease measurement or MRD) is a powerful tool to identify patients at high risk of relapse. Currently, MRD can be assessed by direct detection of leukemic cells (using flow cytometry). This technique is not very precise and cannot be used for all patients. Another MRD measurement strategy involves detecting disease-specific genetic events (gene mutations or chromosomal abnormalities) known as molecular MRD. However, molecular MRD can only be used in about half of the patients, who have particular genetic abnormalities for which specific monitoring tools have been developed. The other half of the patients currently lack an appropriate tool for molecular MRD monitoring.<\/p>\n

Over the last 10 years, technical progress has enabled the identification of several mutations in a vast majority of patients. Theoretically, monitoring these mutations is possible to evaluate molecular MRD. The techniques usually employed do not allow for such evaluation. High-precision next-generation sequencing techniques (called error-corrected NGS) are theoretically suitable. These techniques, which allow the precise detection of any mutation, have been developed especially for monitoring MRD in adult AML. They have shown their usefulness in identifying patients at high risk of relapse, complementing MRD techniques in flow cytometry.<\/p>\n

The researchers’ project is to evaluate the NGS-based MRD monitoring technique in pediatric AML. To do this, Dr. Hirsch’s team will first determine the complete genetic characteristics of the patients at diagnosis and develop a specific tool to monitor all identified genetic mutations by NGS. This MRD measurement will be done after one and two rounds of chemotherapy. The researchers will then assess whether the persistence of a high level of MRD by NGS is associated with a higher relapse rate and if this measurement indeed provides additional value compared to flow cytometry MRD techniques. This study will be conducted using cells collected at diagnosis and after chemotherapy in children treated under the national and international protocols Myechild01, Conect AML, and ALARM3 (project funded in 2023 by Fight Kids Cancer). This project should provide new molecular MRD monitoring methods for nearly all patients and identify those at the highest risk of relapse. This should allow for better treatment adaptation in the long term.<\/p>\n

Trial Follow-up:<\/strong><\/h2>\n

Start Date: 2024<\/p>\n

Project Summary<\/strong><\/h3>\n