Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities.
BACKGROUND
Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years.


METHODS
The authors investigated whether treatment with hypomethylating agents (5-azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46%] with AML [>or=20% blasts]; 44 [54%] with high-risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (>or=3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine-based regimens in 72% and other regimes in 28%).


RESULTS
The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37-85 years and 19-89 years). Thirty-three (41%) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35%) in the chemotherapy group (P=.395). With a median follow-up of 51 weeks (range, 12-101 weeks) and 40 weeks (range, 5-128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P=.153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P=.019).


CONCLUSIONS
Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities.
Ravandi
Farhad
F
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. fravandi@mdanderson.org
Issa
Jean-Pierre
JP
Garcia-Manero
Guillermo
G
O'Brien
Susan
S
Pierce
Sherry
S
Shan
Jianqin
J
Borthakur
Gautam
G
Verstovsek
Srdan
S
Faderl
Stefan
S
Cortes
Jorge
J
Kantarjian
Hagop
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5; D000077209:Decitabine; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine