title: Results of decitabine therapy in the accelerated and blastic phases of chronic myelogenous leukemia.
abstract: The aim of the study was to evaluate the activity of decitabine, a hypomethylating agent, in the treatment of patients with chronic myelogenous leukemia (CML) in transformation. Thirty-seven patients with CML in blastic (20 patients) or accelerated phases (17 patients) were treated. Their median age was 52 years; 36 had Philadelphia chromosome-positive disease. Decitabine was given at 100 mg/m2 over 6 h every 12 h x 10 doses (1000 mg/m2) to 13 patients, and at 75 mg/m2 over 6 h every 12 h x 10 doses (750 mg/m2) to 24 patients. In blastic phase, two patients (10%) achieved a complete hematologic response (one with Ph suppression), and three (15%) had a hematologic improvement (marrow CR, platelets <100 x 10[3]/microl), 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 improvement, and two (12%) had a partial hematologic response, for an overall response rate of 53%. Prolonged myelosuppression was the most significant side-effect. The median time to recovery of granulocytes above 500/microl was 48 days, and to recovery of platelets above 30 x 10(3)/microl, 31 days. Febrile episodes occurred in 25 patients (68%) including documented infections in 17 patients (46%). Decitabine has promising activity in CML. The most significant side-effect is prolonged myelosuppression. Decitabine may show activity in other myeloid disorders such as acute myeloid leukemia and myelodysplastic syndrome, as well as in other hematologic malignancies, alone or with other drug combinations. Its value in the context of stem cell support should also be investigated.
authors.affiliation: Department of Hematology, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: S M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: E
authors.initials: E
authors.lastname: Estey
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: S
authors.initials: S
authors.lastname: Kornblau
authors.forename: M B
authors.initials: MB
authors.lastname: Rios
authors.forename: D
authors.initials: D
authors.lastname: de Vos
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy*; D000077209:Decitabine; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine