Acute Myeloid Leukemia, Genetic Predisposition to Disease
Conditions
Brief summary
Pediatric acute myeloid leukemias are disease with poor prognosis (overall survival of 60-75%) and high relapse rate of 35-45% require further understanding of the underlying biological mechanisms. The main objective of this study is to establish a biological collection to evaluate the genomic profiling of leukemic cells from primary blasts at diagnosis and/or relapse to improve identification of the main genetic hits involved in resistance and could predict a high risk of relapse. Other objectives include the study of bone marrow mesenchymal stem cells and ex vivo drug testing.
Interventions
OTHERCollection of blood sample of bone marrow (cohort 1)
* 3 additional tubes of blood sample (cohort 1), at diagnosis and upon relapse if relapse occurs * Bone marrow aspirate : 3 additional tubes (cohort 1), at diagnosis and upon relapse if relapse occurs
OTHERCollection of blood sample of bone marrow (cohort 2 and 3)
* 1 additional tube of blood sample (cohort 2 and 3 at inclusion) * Bone marrow aspirate: 1 additional tube (cohort 2 and 3 at inclusion)
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
* 0-25 years old * Newly diagnosed de novo or secondary Acute Myeloid Leukemia (AML) or * Relapsed or refractory AML or * Patients with genetic predisposition to develop AML or * Patients without haematological malignancy nor AML genetic predisposition syndrome who undergo bone marrow aspirate as part of standard of care * Signed informed consent of parents for patients aged less than 18 years old or signed informed consent of the patient for patients aged 18 and over.
Exclusion criteria
* Refuse to participate * Chronic myeloid leukemia (CML) * Lack of health insurance (French social security) * Under protection (tutelle, curatelle or sauvegarde de justice) * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of somatic mutations in leukemic cells between diagnosis and relapse identified by Next-Generation Sequencing (NGS) | Up to 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival (EFS) | Up to 5 years | Event Free Survival (EFS) is defined as the time from start of chemotherapy to failure, relapse, or death which ever occurs first |
| Disease Free Survival (DFS) | Up to 5 years | Disease Free Survival (DFS) is defined as the time from remission status to relapse or death. |
| Number of mutations identified by WGS | Up to 5 years | Number of mutations identified by Whole-Genome-Sequencing (WGS) as compared to Next-Generation Sequencing (NGS) in leukemic cells |
| Expression profile (transcriptome) of mesenchymal stem cells | Up to 5 years | Expression profile (transcriptome) of mesenchymal stem cells at AML diagnosis and relapse compared to age matched controls without AML |
| Engraftment rate of primary leukemic cells | Up to 5 years | Engraftment rate of primary leukemic cells in Patient-derived xenografts (PDX) or other experimental models |
| Matched rate of genetic mutational (or expression) profile between derived cells from experimental models to primary leukemic cells | Up to 5 years | — |
| Comparison of LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | — |
| Cumulative incidence of relapse according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | Cumulative incidence of relapse according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse |
| EFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | Event Free Survival according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse |
| Cumulative incidence of relapse (CIR) from remission status. | Up to 5 years | Relapse is defined as: Bone marrow blasts ≥ 5% and/or evidence of extramedullary disease |
| Ex vivo multidrug testing profile of leukemic primary blasts | Up ot 5 years | Comparison of ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse |
| Cumulative incidence of relapse according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Up to 5 years | — |
| EFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Up to 5 years | Event-Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse |
| DFS according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse | Up to 5 years | Disease Free Survival according to ex vivo multidrug testing profile of leukemic primary blasts at diagnosis and relapse |
| Mutational profile of patients | Up ot 5 years | Comparison of mutational profile of patients with a predisposition syndrome compared to mutational profile of patients with AML at diagnosis and relapse |
| Percentage of MRD clearance | Up to 5 years | MRD clearance is defined as MRD below 10-3 Evaluated by flow cytometry and high sensitivity NGS (defined as MRD below 10-4) after each chemotherapy course |
| Cumulative incidence of relapse according to MRD clearance | Up to 5 years | Evaluated by flow cytometry at a sensitivity threshold of 10-3 |
| EFS according to MRD clearance | Up to 5 years | Evaluated by flow cytometry at a sensitivity threshold of 10-3 |
| DFS according to MRD clearance | Up to 5 years | Evaluated by flow cytometry at a sensitivity threshold of 10-3 |
| DFS according to LSC signature profile of leukemic primary blasts at diagnosis and at relapse | Up to 5 years | Disease-Free Survival (DFS) according to Leukemic Stem Cell (LSC) signature profile of leukemic primary blasts at diagnosis and at relapse |
Countries
France
Contacts
Primary ContactArnaud PETIT, Pr
Backup ContactJérôme Lambert, Pr
Outcome results
None listed