Project: Integration of genetic biomarkers and early Minimal Residual Disease to improve risk stratification and cure in childhood Acute Lymphoblastic Leukemia

Acronym	TRANSCALL2 (Reference Number: transcan-fp-189)
Project Topic	Background, rationale Childhood acute lymphoblastic leukemia (ALL) can be cured in about 85% of patients, mainly by the application of intensive combination chemotherapy regimens. Treatment intensity is adjusted according to a limited number of prognostic factors known to predict the risk of relapse. Yet significant numbers of patients still die due to recurrent disease or the toxicity of treatment. Long-term effects of treatment are increasingly acknowledged as a lifetime burden for the health of children cured from ALL. Hence better personalized adjustment of therapy is urgently needed. Hypothesis The use of minimally invasive methods to screen the childhood ALL population for new molecular markers at diagnosis and the combination of genetic information with MRD monitoring in the early treatment phases, will allow the improvement of risk stratification and subsequent clinical decision making for improved personalized precision treatment of children and adolescents with ALL. Aims The Research plan comprises 5 related work packages: 1) Infrastructure and methods; 2) New biomarkers in precursor B-cell ALL; 3) New biomarkers in precursor T-cell ALL; 4) Clinical impact of host genetic heterogeneity; 5) Circulating ‘free’ DNA for MRD monitoring in serum. Methods Our previously funded TRANSCALL project successfully demonstrated the feasibility to validate new prognostic factors thanks to the multidisciplinary competence of scientists, clinicians and statisticians. Advanced molecular biology competences (including NGS, whole genome tests and highly sensitive quantitative PCR) as well as integration with highly curated data management of patients enrolled in AIEOP-BFM and EORTC protocols will be attained.. Expected results and potential impact Having in the same network a strong scientific rationale, similar clinical protocol, a large prospectively treated patient cohort, availability of samples and access to targeted drugs as well as optimal technical skills, we are in the position to design better stratification of children in clinical protocols, and provide targets for clinically valid alternative therapeutic strategies. This project offers a perfect opportunity to extensively apply the concept of personalized medicine in pediatric ALL and is fully adherent to the guidelines of the call and the needs of the European Health System concerning diagnostic suitability. This new stratification and personalized therapy will allow to spare excessive hospitalization of patients, including the need for bone marrow transplantation; as well as the medium to reduce long-term side effects of high-dose chemotherapy. For the health systems, this will mean reducing the excessive costs associated with avoidable medical practices using valid substitute therapies.
Network	TRANSCAN-2
Call	Third Joint Transnational Call (JTC 2016)

Project partner

Number	Name	Role	Country
1	Università di Milano-Bicocca	Coordinator	Italy
2	Azienda Socio Sanitaria Territoriale (ASST) di Monza	Partner	Italy
3	Hannover Medical School	Partner	Germany
4	University of Heidelberg	Partner	Germany
5	Sheba Medical Center	Partner	Israel
6	Robert Debré, Université Paris-Diderot	Partner	France