RESULTS OF DECITABINE THERAPY IN THE ACCELERATED AND BLASTIC PHASES OF CHRONIC MYELOGENOUS LEUKEMIA

The aim of the study was to evaluate the activity of decitabine, a hyp omethylating agent, in the treatment of patients with chronic myelogen ous leukemia (CML) in transformation. Thirty-seven patients with CML i n blastic (20 patients) or accelerated phases (17 patients) were treat ed. Their median age was 52 years; 36 had Philadelphia chromosome-posi tive disease. Decitabine was given at 100 mg/m(2) Over 6 h every 12 h x 10 doses (1000 mg/m(2)) to 13 patients, and at 75 mg/m(2) over 6 h e very 12 h x 10 doses (750 mg/m(2)) to 24 patients. In blastic phase, t wo patients (10%) achieved a complete hematologic response (one with P h suppression), and three (15%) had a hematologic improvement (marrow CR, platelets <100 x 10(3)/mu l), for an overall response rate of 25%. In accelerated phase, six patients (35%) returned to a second chronic phase (two with Ph suppression), one (6%) had a hematologic improveme nt, and two (12%) had a partial hematologic response, for an. overall response rate of 53%. Prolonged myelosuppression was the most signific ant side-effect. The median time to recovery of granulocytes above 500 /mu l was 48 days, and to recovery of platelets above 30 x 10(3)/mu l, 31 days. Febrile episodes occurred in 25 patients (68%) including doc umented infections in 17 patients (46%). Decitabine has promising acti vity in CML. The most significant side-effect is prolonged myelosuppre ssion. Decitabine may show activity in other myeloid disorders such as acute myeloid leukemia and myelodysplastic syndrome, as well as in ot her hematologic malignancies, alone or with other drug combinations. I ts value in the context of stem cell support should also be investigat ed.