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

Grovdal, Michael; Karimi, Mohsen; Khan, Rasheed; Aggerholm, Anni; Antunovic, Petar; Astermark, Jan LU ; Bernell, Per; Engstrom, Lena-Maria; Kjeldsen, Lars and Linder, Olle, et al. (2010) In British Journal of Haematology 150(3). p.293-302
Abstract
P>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... (More)
P>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 center dot 5 months, > 24 months in 17% of the patients, and 18-30 center dot 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 center dot 003). 5-azacytidine treatment, at a dose of 60 mg/m2 was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9 center dot 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. (Less)
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Contribution to journal
publication status
published
subject
keywords
therapy, maintenance, clinical studies, myelodysplastic syndrome, azacytidine, DNA-methylation
in
British Journal of Haematology
volume
150
issue
3
pages
293 - 302
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000279836800004
  • scopus:77954581656
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2010.08235.x
language
English
LU publication?
yes
id
93b97906-8bef-46e5-9b5d-192710b5e103 (old id 1657536)
date added to LUP
2010-08-31 10:37:29
date last changed
2018-05-29 09:42:32
@article{93b97906-8bef-46e5-9b5d-192710b5e103,
  abstract     = {P>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 center dot 5 months, > 24 months in 17% of the patients, and 18-30 center dot 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 center dot 003). 5-azacytidine treatment, at a dose of 60 mg/m2 was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9 center dot 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.},
  author       = {Grovdal, Michael and Karimi, Mohsen and Khan, Rasheed and Aggerholm, Anni and Antunovic, Petar and Astermark, Jan and Bernell, Per and Engstrom, Lena-Maria and Kjeldsen, Lars and Linder, Olle and Nilsson, Lars and Olsson, Anna and Holm, Mette S. and Tangen, Jon M. and Wallvik, Jonas and Oberg, Gunnar and Hokland, Peter and Jacobsen, Sten Eirik W and Porwit, Anna and Hellstrom-Lindberg, Eva},
  issn         = {0007-1048},
  keyword      = {therapy,maintenance,clinical studies,myelodysplastic syndrome,azacytidine,DNA-methylation},
  language     = {eng},
  number       = {3},
  pages        = {293--302},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  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},
  url          = {http://dx.doi.org/10.1111/j.1365-2141.2010.08235.x},
  volume       = {150},
  year         = {2010},
}