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Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine.
- Source :
-
British journal of haematology [Br J Haematol] 2001 Aug; Vol. 114 (2), pp. 349-57. - Publication Year :
- 2001
-
Abstract
- Decitabine (5-aza-2'-deoxycytidine) acts as a powerful demethylating agent in vitro. Clinically, low-dose decitabine ameliorates cytopenias including induction of trilineage responses in approximately 50% of patients with high-risk myelodysplastic syndrome (MDS). We examined the incidence and kinetics of cytogenetic responses to decitabine in these patients. Of 115 successfully karyotyped patients, 61 (53%) had clonal chromosomal abnormalities prior to treatment. Major cytogenetic responses were observed in 19 patients (31% of those with abnormal cytogenetics, 17% of all patients by intention-to-treat) after a median of three courses (range, 2-6) until best cytogenetic response. Progressive decrease of the abnormal clone over time was also determined using fluorescence in situ hybridization (FISH) analysis in two patients. Median duration of cytogenetic responses was 7.5 months (range, 3-15). Analysis of response by the International Prognostic Scoring System (IPSS) cytogenetic risk groups revealed three out of five cytogenetic responses (60%) in the IPSS 'low-risk' group, 6 out of 30 with 'intermediate risk' (20%) and 10 out of 26 in the 'high-risk' group (38%). Median survival in these cytogenetic subgroups was 30, 8 and 13 months respectively. The relative risk of death in patients achieving a major cytogenetic response was 0.38 (95% confidence interval 0.17-0.88) compared with patients in whom the cytogenetically abnormal clone persisted (P = 0.0213). In conclusion, repeated courses of low-dose decitabine induce cytogenetic remissions in a substantial number of elderly MDS patients with pre-existing chromosomal abnormalties; these are associated with improved survival compared with patients in whom the cytogenetically abnormal clone persists. Patients with 'high-risk' chromosomal abnormalities may particularly benefit from this treatment.
- Subjects :
- Adult
Aged
Aged, 80 and over
Anemia, Refractory drug therapy
Anemia, Refractory genetics
Anemia, Refractory mortality
Anemia, Refractory, with Excess of Blasts drug therapy
Anemia, Refractory, with Excess of Blasts genetics
Anemia, Refractory, with Excess of Blasts mortality
Anemia, Sideroblastic drug therapy
Anemia, Sideroblastic genetics
Anemia, Sideroblastic mortality
Azacitidine analogs & derivatives
Chromosome Aberrations
Chromosome Disorders
Decitabine
Drug Administration Schedule
Female
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Leukemia, Myelomonocytic, Chronic drug therapy
Leukemia, Myelomonocytic, Chronic genetics
Leukemia, Myelomonocytic, Chronic mortality
Male
Middle Aged
Myelodysplastic Syndromes genetics
Myelodysplastic Syndromes mortality
Risk
Survival Rate
Antimetabolites, Antineoplastic therapeutic use
Azacitidine therapeutic use
Myelodysplastic Syndromes drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1048
- Volume :
- 114
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 11529854
- Full Text :
- https://doi.org/10.1046/j.1365-2141.2001.02933.x