This is an open-label, randomized, multicenter, phase III study

Patients with baseline Hb comprised between 9 and 10.5g/dl will be randomized to receive EPO Alfa 60000 UI/week for at least 12 weeks:

• Either at diagnosis Or
• at the Hb threshold chosen for RBC transfusions (must be < 9g/dl)

in this trial we will compare the early introduction of EPO alfa to the delayed introduction in lower risk MDS with non RBC transfusion dependent anemia.

At enrollment patients will be randomised in the 2 arms (early and delayed start of EPO alfa).

Treatment Regimen Epoetin alfa 60000 UI/week for at least 12 weeks

1. Early onset arm: early onset of EPO ALFA 60000 IU/week , at patient inclusion
2. Delayed onset arm: late introduction of EPO ALFA 60000 IU/week, whenever the patient reaches the level chosen RBC transfusions (based on age, comorbidities, anticipated tolerance of anemia).

Inclusion Criteria:

1. Age ≥ 18 years
2. MDS according to WHO 2016 criteria, with low or int 1 classical IPSS
3. Non-RBC transfusion dependent anemia
4. Hb level between 9 and 10.5g/dl (at the center's lab)
5. Hb level should be at least 1g/dl higher than the Hb threshold chosen to start RBC transfusions based on age, comorbidities and predicted clinical tolerance of anemia (this transfusion threshold should be chosen between 8 and 9g/dl)
6. Serum EPO level <500U/l
7. No other cause of anemia (including iron deficiency, vitamin B12 or B9 deficiency, hemolysis, hypothyroidism….)
8. Performance status <=2

Exclusion Criteria:

1. Higher risk MDS (IPSS intermediate-2 or high)
2. Del 5q
3. Baseline Hemoglobin level > 10.5 g/dl or <9g/dl
4. Transfusion threshold (based on age , comorbidities…) >9g/dl
5. Transfusion threshold less than 1 g/dl below baseline Hb level
6. RBC transfusion dependence. Patients may have received only one transfusion series for MDS prior to inclusion
7. CMML , if >10 % BM blasts or WBC>13.000/mm3
8. Uncontrolled hypertension
9. Uncontrolled cardiovascular disease including angina pectoris or cardiac failure
10. Renal failure: Creatinine clearance<40ml/min (using MDRD formula)
11. Pregnancy (positive bettaHCG) or nursing