title: Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy.
abstract: This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.
authors.affiliation: Division of Haematology, Department of Medicine, Centre for Experimental Haematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. michael.grovdal@ki.se
authors.forename: Michael
authors.initials: M
authors.lastname: Grövdal
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karimi
authors.forename: Rasheed
authors.initials: R
authors.lastname: Khan
authors.forename: Anni
authors.initials: A
authors.lastname: Aggerholm
authors.forename: Petar
authors.initials: P
authors.lastname: Antunovic
authors.forename: Jan
authors.initials: J
authors.lastname: Astermark
authors.forename: Per
authors.initials: P
authors.lastname: Bernell
authors.forename: Lena-Maria
authors.initials: LM
authors.lastname: Engström
authors.forename: Lars
authors.initials: L
authors.lastname: Kjeldsen
authors.forename: Olle
authors.initials: O
authors.lastname: Linder
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Anna
authors.initials: A
authors.lastname: Olsson
authors.forename: Mette S
authors.initials: MS
authors.lastname: Holm
authors.forename: Jon M
authors.initials: JM
authors.lastname: Tangen
authors.forename: Jonas
authors.initials: J
authors.lastname: Wallvik
authors.forename: Gunnar
authors.initials: G
authors.lastname: Oberg
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
authors.forename: Sten E
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Anna
authors.initials: A
authors.lastname: Porwit
authors.forename: Eva
authors.initials: E
authors.lastname: Hellström-Lindberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000627:therapeutic use*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D009503:Neutropenia / Q000139:chemically induced; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D001374:Azacitidine