High Risk Myelodysplasia Treated by Azacytidine : Genetic and Epigenetic (MYRAGE)

High Risk Myelodysplasia Treated by Azacytidine : Genetic and Epigenetic (MYRAGE)

Myelodysplastic syndromes (MDS) are the most frequent myeloid neoplasms in Western Countries.They mainly affect patients aged 65 years or older. This is a very heterogenous group of diseases, which prognosis is evaluated with International Prognosis Scoring System. High risk MDS present with high frequency of transformation into acute myeloid leukemia. Treatment of high risk MDS often is based on hypomethylating agents, such as 5'-azacytidine (Azacytidine), with a complete response in approximativel 20% of cases..

This treatment is based on 4-week cycles, with daily injection during the first week and rest during the 3 next weeks of the cycle.

Azacytidine efficacy is commonly evaluated with clinical and biological parameters determined by the International Working Group 2006. These parameters are usually evaluated after at least 6 cycles of treatments.

There is a response with Azacytidine treatment in 60% of cases, including 40% of partial responses and 20% of complete responses. In 40% of patients, there is no response, which means that the disases is stable or in progression under therapy.

In this regard, early evaluation of treatment response is an issue. We want to improve our knowledge about early response criteria in Azacytidine-treated high-risk MDS, focusing on SMD with excess blasts, which represent 30 to 40% of total MDS.

Then, the investigator team want to compare DNA methylation profile at diagnosis and after 3 cycles of Azacytidine treatment.

Main objective :

Identify DNA methylation profiles related to response to Azacytidine therapy, after only 3 cycles of treatment, in high risk MDS with excess blasts.

Secondary objective :

Identify at diagnosis DNA methylation profiles that are predicitive of response to Azacytidin, in high risk MDS with excess blasts.

Pre-inclusion Criteria:

• patient benefiting from social welfcare
• patient followed at the University Hospital of Nancy
• patient aged 18 years or older
• patient informed on research organization and having signed an informed pre-inclusion consent
• No personal history of myelodysplastic syndrome
• clinical exam adapted to research
• one or more blood cytopenia

Inclusion Criteria:

• patient benefiting from social welfcare
• patient followed at the University Hospital of Nancy
• patient aged 18 years or older
• patient informed on research organization and having signed an informed inclusion consent
• definitive diagnosis of high risk myelodysplastic syndrome with excess blasts
• eligibility to an Azacytidine therapy as first-line treatment

Exclusion Criteria:

• personal history or current other cancer
• immediate acute myeloid leukemia
• personal history of demethylation treatment
• pregnant or breast feeding women
• life-theatening condition
• guardianship
• imprisoned patients