title: Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials.
abstract: Diagnostic karyotype provides the framework for risk-stratification schemes in acute myeloid leukemia (AML); however, the prognostic significance of many rare recurring cytogenetic abnormalities remains uncertain. We studied the outcomes of 5876 patients (16-59 years of age) who were classified into 54 cytogenetic subgroups and treated in the Medical Research Council trials. In multivariable analysis, t(15;17)(q22;q21), t(8;21)(q22;q22), and inv(16)(p13q22)/t(16;16)(p13;q22) were the only abnormalities found to predict a relatively favorable prognosis (P < .001). In patients with t(15;17) treated with extended all-trans retinoic acid and anthracycline-based chemotherapy, additional cytogenetic changes did not have an impact on prognosis. Similarly, additional abnormalities did not have a significant adverse effect in t(8;21) AML; whereas in patients with inv(16), the presence of additional changes, particularly +22, predicted a better outcome (P = .004). In multivariable analyses, various abnormalities predicted a significantly poorer outcome, namely abn(3q) (excluding t(3;5)(q25;q34)), inv(3)(q21q26)/t(3;3)(q21;q26), add(5q)/del(5q), -5, -7, add(7q)/del(7q), t(6;11)(q27;q23), t(10;11)(p11 approximately 13;q23), other t(11q23) (excluding t(9;11)(p21 approximately 22;q23) and t(11;19)(q23;p13)), t(9;22)(q34;q11), -17, and abn(17p). Patients lacking the aforementioned favorable or adverse aberrations but with 4 or more unrelated abnormalities also exhibited a significantly poorer prognosis (designated "complex" karyotype group). These data allow more reliable prediction of outcome for patients with rarer abnormalities and may facilitate the development of consensus in reporting of karyotypic information in clinical trials involving younger adults with AML. This study is registered at http://www.isrctn.org as ISRCTN55678797 and ISRCTN17161961.
authors.affiliation: Department of Medical and Molecular Genetics, King's College London School of Medicine and Department of Haematology, Guy's & St. Thomas' NHS Foundation Trust, London, United Kingdom. david.grimwade@genetics.kcl.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Grimwade
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: Helen
authors.initials: H
authors.lastname: Walker
authors.forename: Stephen
authors.initials: S
authors.lastname: Chatters
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D016026:Bone Marrow Transplantation; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3