PMID- 11529854
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 114
IP  - 2
DP  - 2001 Aug
TI  - Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose 
      treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine.
PG  - 349-57
AB  - 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.
FAU - Lubbert, M
AU  - Lubbert M
AD  - Department of Medicine, Division of Haematology/Oncology, University of Freiburg 
      Medical Centre, Freiburg, Germany. luebbert@mm11.ukl.uni-freiburg.de
FAU - Wijermans, P
AU  - Wijermans P
FAU - Kunzmann, R
AU  - Kunzmann R
FAU - Verhoef, G
AU  - Verhoef G
FAU - Bosly, A
AU  - Bosly A
FAU - Ravoet, C
AU  - Ravoet C
FAU - Andre, M
AU  - Andre M
FAU - Ferrant, A
AU  - Ferrant A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 776B62CQ27 (Decitabine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia, Refractory/drug therapy/genetics/mortality
MH  - Anemia, Refractory, with Excess of Blasts/drug therapy/genetics/mortality
MH  - Anemia, Sideroblastic/drug therapy/genetics/mortality
MH  - Antimetabolites, Antineoplastic/*therapeutic use
MH  - Azacitidine/analogs & derivatives/*therapeutic use
MH  - Chromosome Aberrations
MH  - Chromosome Disorders
MH  - Decitabine
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myelomonocytic, Chronic/drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*drug therapy/genetics/mortality
MH  - Risk
MH  - Survival Rate
EDAT- 2001/09/01 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/09/01 10:00
PHST- 2001/09/01 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/09/01 10:00 [entrez]
AID - bjh2933 [pii]
AID - 10.1046/j.1365-2141.2001.02933.x [doi]
PST - ppublish
SO  - Br J Haematol. 2001 Aug;114(2):349-57. doi: 10.1046/j.1365-2141.2001.02933.x.