title: Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies.
abstract: We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK(+) patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK(+). MK(+) patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of -5/5q-, -7, 7q-, abnl(12p), abnl(17p), -18/18q-, -20/20q-, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)-related cytogenetic abnormalities (P < .0001, each); and NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and tyrosine kinase domain mutations (P = .02) were less frequent in MK(+). Response to induction therapy and overall survival in MK(+) patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients, allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival.
authors.affiliation: Department of Internal Medicine III, University Hospital of Ulm, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kayser
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Köhne
authors.forename: Heinz A
authors.initials: HA
authors.lastname: Horst
authors.forename: Gerhard
authors.initials: G
authors.lastname: Held
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Sibylla
authors.initials: S
authors.lastname: Wilhelm
authors.forename: Mathias
authors.initials: M
authors.lastname: Rummel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Katharina
authors.initials: K
authors.lastname: Götze
authors.forename: David
authors.initials: D
authors.lastname: Nachbaur
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Daniela
authors.initials: D
authors.lastname: Späth
authors.forename: Carina
authors.initials: C
authors.lastname: Morlok
authors.forename: Veronica
authors.initials: V
authors.lastname: Teleanu
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000401:mortality / Q000628:therapy; D000090243:Nucleophosmin; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult