Leukaemia (Acute Lymphoblastic), Leukaemia (Acute Myeloid), Myelodysplastic Syndrome
Conditions
Keywords
VIDAZA, CSH graft, haematopoietic stem cell, natural killer cells, NK Cells
Brief summary
The aim of the ENKLA-M study is to collect samples from patients with acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), and myelodysplastic syndrome (MDS) to study the evolution of blast phenotype (NK receptor ligands and adhesion molecules) and the biology of patients' NK cells). To do this, blood and bone marrow samples will be collected from patients at diagnosis in order to characterize: (I) the phenotype of ALL and AML blasts with respect to NK receptor ligands and adhesion molecules; (II) the phenotypic profile of NK cells, (III) to further characterize the NK cell repertoire dynamics over time (day 30, day 60, day 90, 6 months, and 1 year), focusing on NK cell populations identified in healthy individuals as particularly effective against leukemia, by defining their phenotypic and transcriptomic profiles; and (IV) the impact of azacitidine (AZA) and donor lymphocyte infusions (DLI) on the biology of NK cells in transplanted patients. Clinical data and KIR/HLA genetic profiles will be used to analyze all NK phenotypic and functional data, with the aim of better defining: (i) the key molecular interactions between NK cells and leukemic cells; (ii) markers of NK cell anti-leukemic efficacy during hematopoietic reconstitution; and (iii) whether AZA/DLI treatment enhances the functional potential of NK cells via KIR-HLA interaction, thereby improving their effectiveness against residual disease.
Interventions
OTHERBone marrow sampling (during routine care)
Bone marrow sample (1 ml)
OTHERBlood samples (during routine care)
3 tubes of 10 ml per visit
Sponsors
Nantes University Hospital
EFS CPDL: French Blood Establishment Centre-Pays de la Loire
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients diagnosed with acute myeloid leukaemia (LAM), acute lymphoblastic leukaemia (LAL) or myelodysplastic syndrome (SMD). * Adult patients receiving a HSC transplant. * Adult patients receiving or not AZA treatment after transplantation. * Patients who have signed a consent form. * Patients affiliated with a social security system.
Exclusion criteria
* Minors, * Pregnant and/or breastfeeding women * Adult patients under guardianship, * Protected persons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Define the KIR and HLA genetic markers associated with an anti-leukaemic response mediated by NK cells at different stages in the progression of Acute lymphocytic leukaemia or a myalodysplasia syndrome. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Assess the functional potential of different NK cell populations at diagnosis of acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndrome (at each possible relapse of the patient). | 12 months |
| Assess NK cell reconstitution during transplant of hematopoietic stem cells. | 12 months |
| Assess the impact of the hypomethylating agent AZA used to prevent relapse after allogeneic transplantation for acute myeloid leukaemia or myelodysplastic syndrome on NK cells. | 12 months |
| Assess the impact of Donor Lymphocyte Injection used in the prevention of post-allogeneic transplant relapse on NK cells. | 12 months |
Countries
France
Contacts
CONTACTSponsor department
PRINCIPAL_INVESTIGATORPatrice CHEVALLIER
Nantes University Hospital
Outcome results
None listed