A Phase II randomized multicenter study to assess the efficacy of lenalidomide with or without erythropoietin and granulocyte-colony stimulating factor in patients with low and intermediate-1 risk myelodysplastic syndrome.

1. Patients with MDS classified as:

RA, RARS and RAEB (with <10% myeloid blasts), CMML (with <10% myeloid blasts), according to FAB, or;

RA, RARS, RCMD, RCMD-RS, RAEB-1, MDS-U according to WHO, or;

patients with MPD/MDS (CMML-1 according to WHO) with a WBC <= 12x10^9/l, with an IPSS <= 1.0.

2. Hb <= 6.2 mmol/l (10.0 g/dl) or Hb <= 7.2 mmol/l and ANC <= 1.0x10^9/l or red blood cell transfusion dependent;

3. Age >= 18 years;

4. WHO performance status 0-2;

5. Patient not previously treated with Epo/G-CSF, or failure of response or relapse after hematological improvement or disease progression to maximal RAEB-1 after previous therapy with Epo/G-CSF;

6. Serum creatinin < 150 µmol/l;

7. Serum billirubin < 25 µmol/l and ASAT, ALAT and Alkaline phosphatase < 2.5 times the upper limit of normal, except if related to disease;

8. The patient must give written informed consent;

9. Negative pregnancy test within 7 days prior to start of study drug, if applicable;

10. Patient (all men, pre-menopausal women) agrees to use adequate contraceptive methods;

11. Serum erythropoietin level > 200 U/l or <= 200 U/l if failure of response or loss of hematological improvement or disease progression to maximal RAEB-1 after prior standard therapy with Epo/G-CSF; Epo/G-CSF should be stopped at least 1 month before randomization.

1. Severe cardiac, pulmonary, neurologic, metabolic or psychiatric diseases or active malignancies;

2. Anemia due to other causes than MDS including iron, B12 and folate deficiencies, auto-immune hemolysis and/or paroxysmal noctural hemoglobinuria (PNH);

3. Hypoplastic MDS;

4. High predictive score (score 0 or 1) to respond on standard treatment with Epo/G-CSF according to guidelines;

5. Active uncontrolled infection;

6. Absolute neutrophil count (ANC) < 0.5x10^9/l;

7. Patients dependent on platelet transfusions or with platelet counts < 25x10^9/l or patients with active bleeding;

10. Patients treated with biological response modifiers (i.e. growth factors, immunosuppressive agents and/or chemotherapy) within 1 month prior to randomization;

11. Lactating women;

12. Prior treatment with lenalidomide;

13. Prior CTCAE >= grade 3 allergic reaction/hypersensitivity to thalidomide;

14. Prior CTCAE >= grade 3 rash/blistering while taking thalidomide
15. Prior CTCAE >= grade 3 allergic/hypersensitivity to Epo and/or G-CSF