La terapia demetilante con 5-azacitidina nelle sindromi mielodisplastiche: esperienza clinica del Nostro Istituto e correlazione con i dati biologici

Based on the evidence of literature (Fenaux 2009; Lyons 2009), from September 2004, in our Institute, 57 patients (pts) with Myelodysplastic Syndrome were treated (MDS) with demethylating therapy. We used 4 different regimens depending on the class of IPSS risk: patients at risk low/int-1 received Azacitidine 75 mg/sqm/day subcutaneously for 5 days/month (AZA 5) for 8 cycles, patients at risk high/int-2 received Azacitidine 50 mg/sqm/day subcutaneously for 10 days/month (AZA 5-2-5) or Azacitidine 75 mg/sqm/day for 7 days/month (AZA 7) until loss of response. On a series total of 57 pts (15 lower risk; 41 higher risk), 87 .7% (50 pts) were evaluable. Among these, responses observed were 68% (34 pts): 14% (7 pts) achieved complete remission (CR) and 54% (27 pts) had a Hematologic Improvement (HI). The assessment of response was performed according to the criteria of the International Working Group 2006 (Cheeson 2006). The main toxicities observed were represented by local skin reactions at the injection site, gastrointestinal toxicity (constipation and/or diarrhea), myelotoxicity, febrile neutropenia, sepsis (3 pts). Among the patients we observed the presence of prolonged hematologic response (? 20 months) in 10 pts (20% of evaluable patients). In addition, thanks to the collaboration with the Department of Human Anatomy, University of Bologna (Prof. L. Cocco, Dr. Follo MY), all patients were evaluated for levels of gene expression and gene methylation of phospholipase PI PLC- àŸ 1. The biological data obtained were correlated with clinical, highlighting the presence of a correlation between the levels of gene expression and mutilation of PI-PLC-àŸ1 and response to therapy with demethylating 5-Azacitidine.