Decitabine Treatment in Higher Risk MDS, CMML and AML Post-MDS Who Failed Azacitidine

5-azacytidine (Vidaza, AZA) and 5-aza-2'-deoxycytidine (Decitabine, DAC) are active in therapy of myelodysplastic syndromes (MDS) probably with different mechanisms of action. Azacitidine is approved by FDA and EMEA and is routinely used in therapy of higher risk MDS in Europe and in the US. Decitabine is a demethylating agent approved for treatment of IPSS INT-2 and high risk MDS by FDA but not yet from EMEA and it seems particularly active in Chronic myelomonocytic leukemia (CMML) and AML of the elderly. Difference in mechanisms of action of these 2 agents have been determined in vitro, involving nuclear acid incorporation, cell cycle and apoptosis, gene and protein expression.

Nine patients (4 RAEB 2, 4 AML, 1 CMML-1) were treated with decitabine 20mg/m2 × 5 days every 28 days as single agent or in association with Gemtuzumab ozogamicin 3 mg/m2 in day 5 and 9. IPSS score at diagnosis was: 1 low, 4 intermediate 1, 4 intermediate 2. All patients received at least 4 cycles of azacitidine 75 mg/mq per seven days every 28, 44% of them reached at least Hematological improvement and received DAC as second line after relapse. Median age was 70 (62–84) and 8/9 were male.

Medical records of 14 patients who received decitabine treatment were reviewed and survival was calculated by the Kaplan Meier method and differences in survival calculated by the log-rank test using SPSS software. Complete remission was defined by normo-cellular bone marrow with <5% blasts and normal Hgb, WBC, and platelet counts, and PR required 50% decrease in blast count, increases in Hgb by >1.5 mmol/L, WBC count by >1000, and platelet count by >50,000. Results: Median overall survival (OS) was 121 days, range 27–586 days. Overall response rate (CR+PR+HI) was 33.3% with mean duration of response was 3.33 months. Mean number of cycles was 4 (range 1–20). Median OS of responder patients was 12 months vs 1 month of non responder patients. OS of patients treated with DAC after AZA-resistance was 2 months vs 4 months of patients relapsed, but who reached at least HI with AZA (p>0.05). Longer history of MDS disease seemed not relevant for outcome. Therapy was well tolerated and only two patients required a long hospitalization (42 and 77 days) for sepsis due to relevant myelosuppression.

Decitabine treatment has some activity in MDS, CMML and AML patients refractory to AZA or who relapsed after initial response to AZA, suggesting that the two supposed hypomethylating agents act via partially different molecular mechanisms.

No relevant conflicts of interest to declare.