Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

Michael Grövdal (1) , Mohsen Karimi (1) , Rasheed Khan (1) , Anni Aggerholm (2) , Petar Antunovic (3) , J Astermark (4) , Per Bernell (5) , Lena-Maria Engström (6) , Lars Kjeldsen (7) , Olle Linder (8) , Lars Nilsson (9) , Anna Olsson (10) , Mette Skov Holm (2) , Jon Magnus Tangen (11) , Jonas Wallvik (12) , Gunnar Öberg (13) , Peter Hokland (2) , Sten Eirik Jacobsen (14) , Anna Porwit (15) , Eva Hellström-Lindberg (1)

1 Department of Medicine, Centre for Experimental Haematology
2 Department of Haematology
3 Department of Haematology
4 Department for Haematology and Coagulation Disorders
5 Department of Haematology
6 Department of Haematology
7 Department of Haematology
8 Department of Medicine
9 Haematopoietic Stem Cell Laboratory and Department of Haematology
10 Department of Haematology
11 Department of Haematology
12 Department of Medicine
13 Department of Haematology
14 Hematopoietic Stem Cell Laboratory and Department of Hematology
15 Department of Pathology

This prospective phase II study is the first to assess feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk MDS, CMML and MDS-AML 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 days until relapse. Promoter-methylation status of CDKN2B (P15), e-cadherin and hypermethylated in cancer 1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved complete remission 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 P15 methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of E-cadherin was significantly associated with low CR rate, early relapse, and short OS (P=0.003). 5-azacytidine treatment in a dose of 60 mg/m2 was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while hemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.

Mots clés: Medicine

Michael Grövdal, Mohsen Karimi, Rasheed Khan, Anni Aggerholm, Petar Antunovic, et al.. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. British Journal of Haematology, 2010, 150 (3), pp.293. ⟨10.1111/j.1365-2141.2010.08235.x⟩. ⟨hal-00552597⟩