The study aims to assess the activity of decitabine in the treatment of CMML.

Inclusion Criteria:

1. Patients aged 18 and older

2. CMML diagnosis according to WHO criteria

3. If WBC<=12000/mm3:IPSS High or INT-2

   If WBC>12000/mm3: at least two of the following criteria:

   • Blast cells>5% in the bone marrow
   • Citogenetic abnormality other then t(5;12) (q33;p13)
   • Anemia (Hb<10g/dl)
   • Thrombocytopenia (Plt<100000/mm3)
   • Splenomegaly(>5cm below costal margin)
   • Extramedullary localization

4. Patients untretaed or previously treated with Hydroxyurea or Imatinib or Etoposide given orally or non intensive chemotherapy or intensive chemotherapy given more thann 3 months befor inclusion

5. Performance Status ECOG 0,1 or 2

6. Estimated life expectancy>=6 months

7. Adequate hepatic function:

   • Total bilirubin < 1.5 times upper limit of normal (except moderate unconjugate hyperbilirubinemia due to intra medullary hemolysis)
   • AST and ALT < 3 times limit of normal

8. Adequate renal function:

   • Serum creatinine < 1.5 times limit of normal
   • Creatinine clearance > 30ml/min

9. Informed consent

10. Negative pregnancy test or adequate contraception methods

Exclusion Criteria:

1. Myeloproliferative/myelodisplastic syndome othe than CMML
2. Acute blastic transformation of CMML with bone marrow blast cells>20%
3. Patients eligible for allogenic bone marrow transplantation with identified donor
4. CMML with t(5;12) o PDGFBR rearrangement
5. Intensive chemotherapy given less than 3 months before
6. Previous treatment with hypomethylating agent
7. Age< 18 years old
8. Pregnancy or breastfeeding
9. Performance Status ECOG>2
10. Estimate life expectancy<6 months
11. HIV infection
12. Chronic active hepatitis secondary to HCV or HBV (HBSAq positive)
13. Serious concomitantsystemic disorders, including active bacterial fungal or viral infection, that in the opinion of the investigator, would compromise the safety of the patient and/or his/her ability to complete the study