Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia
Conditions
Keywords
Myelodysplastic syndrome, Ascorbic acid, Oxidative stress, Preleukemia
Brief summary
Myelodysplastic syndromes (MDS) is a group of heterogeneous diseases characterised by the clonal evolution of dysplastic hematopoietic stem cells. This evolution is associated with accumulation of cytogenetic mutations which leads to acute myeloid leukaemia (AML). Evolution of MDS is also associated with increase of reactive oxygen species (ROS). The increase of ROS is associated with accumulation of cytogenetic mutations. Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body. Studies showed that supplementation with AA can change the proliferation status of MDS cells. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients with myelodysplastic syndromes advanced in their treatment or recently diagnosed during a follow-up of 12 months.
Detailed description
Myelodysplastic syndromes (MDS) is a group of heterogeneous life threatening diseases characterised by the clonal evolution of dysplastic myeloid hematopoietic stem cells. This evolution is initially associated with an excess of apoptosis followed by an excess of proliferation then, after accumulation of cytogenetic mutations, a transformation in acute myeloid leukaemia (AML) can appear. Evolution of MDS is also associated with increase of reactive oxygen species (ROS) . In MDS mice, perturbations of the metabolism of ROS is associated with increases in the number of cytogenetic mutations. Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body. In vitro studies showed that supplementation with AA can change the proliferation status of MDS cells . Guinea pigs with a phenotype with excess of ROS supplemented with AA have less somatic mutations and less MDS. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML. To our knowledge no study have demonstrated the variations of the parameters of the oxidative metabolism during the evolution of MDS. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients diagnosed with MDS in treatment or recently diagnosed during a follow-up of 12 months. During the follow-up a collection of plasma from volunteers and patients will be created for later analysis.
Interventions
OTHERSamples
Blood samples
OTHERQuality of life questionnaire
Questionnaire to assess the quality of life of cancer patients
Sponsors
Tours Autogreffe
Novartis
University Hospital, Tours
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Patients MDS at diagnosis group selection criteria Inclusion Criteria: * Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification * Patient diagnosed for less than 4 months before inclusion * Patient untreated by other means than blood transfusions * Age ≥ 60 years * Patient affiliated to social security scheme * Informed consent signed by the patient
Exclusion criteria
* Previous allogenic stem cell transplantation * Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention * Active inflammatory disease * Patient under legal protection measure * Patient unwilling or who cannot submit to prospective biological follow-up 2. Patients MDS in treatment group selection criteria: Inclusion Criteria: * Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification * Patient not included in patients MDS at diagnosis group * Patient diagnosed for more than 12 months * Treated with hypomethylating agents and/or erythropoiesis-stimulating agents and/or blood transfusions. * Age ≥ 60 years * Patient affiliated to social security scheme * Informed consent signed by the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasmatic ascorbic acid concentration at baseline | month 0 | For all groups: Plasmatic ascorbic acid concentration at first visit (0 month) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasmatic ascorbic acid concentration during follow-up | at 3 months, 6 months and 12 months | For all groups: Plasmatic ascorbic acid concentrations at 6 months and 12 months visits with an extra plasmatic ascorbic acid concentrations at 3 months for patients MDS groups |
| Plasmatic antioxidants concentrations | at 0 months, 6 months and 12 months | For all groups: Plasmatic antioxidants concentrations at 0 months, 6 months and 12 months |
| Complete blood count and blood blasts cells | at 0 month, 3 months, 6 months and 12 months | For patients MDS groups: Complete blood count and blood blasts cells at 0 month, 3 months, 6 months and 12 months |
| Polyunsaturated fatty acids | at 0 month, 3 months, 6 months and 12 months | For patients MDS groups: Polyunsaturated fatty acids at 0 month, 3 months, 6 months and 12 months |
| Collection of plasma | at 0 month, 3 months, 6 months and 12 months | For all groups: Creation of a collection of plasma samples for later analysis at 0 month, 6 months and 12 months with an extra plasma sample at 3 months for patients MDS groups |
| Oxidative stress parameters and number of adverse events | at 3 months, 6 months and 12 months | For patients MDS groups: Oxidative stress parameters at 3 months, 6 months and 12 months and number of adverse events during follow-up |
| Plasmatic ascorbic acid concentration and parameters of iron metabolism | at 0 month and 12 months | For patients MDS groups: Plasmatic ascorbic acid concentration and parameters of iron metabolism at 0 month and 12 months |
| Plasmatic ascorbic acid concentration and quality of life | at 0 month, 3 months, 6 months and 12 months | For patients MDS groups: Plasmatic ascorbic acid concentration and quality of life evaluated by the EORTC QLQ-C30 3rd version at 0 month, 3 months, 6 months and 12 months |
| Collection of frozen cells | 0 month and in case of evolution of the disease | For patients MDS groups: Creation of a collection of frozen cells for DNA analysis at 0 month and in case of evolution of the disease. |
| Plasmatic ascorbic acid concentration and number of adverse events | at 3 months, 6 months and 12 months | For patients MDS groups: Plasmatic ascorbic acid concentration at 3 months, 6 months and 12 months and number of adverse events during follow-up |
Countries
France
Outcome results
None listed