title: Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: results from Cancer and Leukemia Group B 8461.
abstract: To date, neither the clinical significance of isolated trisomy 8, the most frequent trisomy in acute myeloid leukemia (AML), nor the effect of age within a single cytogenetic group has been examined. We report a large cohort of adult trisomy 8 patients and examine whether increasing age within a homogeneous cytogenetic group alters clinical outcome. Characteristics and outcome of patients with isolated trisomy 8 enrolled in the prospective Cancer and Leukemia Group B (CALGB) cytogenetic study CALGB 8461 are described. Isolated trisomy 8 was identified in 42 (3.03%) of 1387 patients enrolled in five CALGB treatment protocols. These patients had a median age of 64 (range, 16-79) years, 50% female proportion, and a low frequency of hepatomegaly (10%) or splenomegaly (10%). Laboratory features included a median white blood count of 7.3 x 10(9)/L, nonspecific French-American-British distribution, with 36% of patients having Auer rods. Treatment outcome was unsatisfactory with a complete remission (CR) rate of 59%, median CR duration of 13.6 months, and median survival of 13.1 months. Older age adversely affected outcome; trisomy 8 patients > or =60 years had both an inferior CR rate (40% versus 88%; P = 0.004) and overall survival (median, 4.8 versus 17.5 months; P = 0.01), as compared with those <60 years of age. Of the patients <60 years of age, only four remain alive, and all received noncytarabine-based intensive chemotherapy, followed in three cases by autologous (n = 2) or allogeneic (n = 1) stem cell transplant in CR1. Adults with AML and isolated trisomy 8 have a poor outcome that is accentuated by increasing age and is rarely cured with cytarabine-based therapy. Alternative investigational treatments should be considered for individuals with this AML subset.
authors.affiliation: Walter Reed Army Medical Center, Washington, DC 20307, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.forename: D
authors.initials: D
authors.lastname: Lawrence
authors.forename: D C
authors.initials: DC
authors.lastname: Arthur
authors.forename: M J
authors.initials: MJ
authors.lastname: Pettenati
authors.forename: R
authors.initials: R
authors.lastname: Tantravahi
authors.forename: M
authors.initials: M
authors.lastname: Qumsiyeh
authors.forename: J
authors.initials: J
authors.lastname: Stamberg
authors.forename: F R
authors.initials: FR
authors.lastname: Davey
authors.forename: C A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015331:Cohort Studies; D003561:Cytarabine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014314:Trisomy
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine