Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome.
BACKGROUND
Therapy for patients with myelodysplastic syndrome (MDS) with hypomethylating agents, like decitabine and 5-azacitidine, has produced favorable results. In this study, the authors update their experience with decitabine in patients with MDS and analyze the cytogenetic response patterns and prognostic factors associated with decitabine therapy.


METHODS
One hundred fifteen patients with higher risk MDS who received treatment with decitabine were reviewed. Patients received decitabine 100 mg/m(2) per course every 4 weeks in 3 different schedules: 1) 20 mg/m(2) intravenously daily x 5, 2) 20 mg/m(2) subcutaneously daily x 5, and 3) 10 mg/m(2) intravenously daily x 10. Decitabine was given for a median of >or=7 courses (range, 1-23 courses).


RESULTS
Overall, 80 patients (70%) achieved a response according to the modified International Working Group criteria (IWG): complete response (CR), 40 patients (35%); partial response, 2 patients (2%); bone marrow CR with or without other hematologic improvements (HI), 26 patients (23%); and other HI, 12 patients (10%). Cytopenias were improved in 50% of patients. The median remission duration was 20 months, and the median survival was 22 months. Mortality was 3% at 6 weeks and 7% at 3 months. In a multivariate analysis, poor prognostic factors for achieving IWG CR were MDS (vs chronic myelomonocytic leukemia), longer duration of MDS, and prior MDS therapy. For survival, independent adverse prognostic factors were chromosome 5 and/or 7 abnormalities, older age, and prior MDS therapy (excluding growth factors).


CONCLUSIONS
The longer term experience with decitabine in MDS was favorable. Pretreatment prognostic factors may predict the outcome of patients who receive decitabine therapy for MDS.
Kantarjian
Hagop M
HM
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
O'Brien
Susan
S
Shan
Jianqin
J
Aribi
Ahmed
A
Garcia-Manero
Guillermo
G
Jabbour
Elias
E
Ravandi
Farhad
F
Cortes
Jorge
J
Davisson
Jan
J
Issa
Jean-Pierre
JP
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D000077209:Decitabine; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine