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Lookup NU author(s): Professor Anthony MoormanORCiD, Professor Christine Harrison FRCPath FMedSci
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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 similar to 13;q23), other t(11q23) (excluding t(9; 11)(p21 similar to 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. (Blood. 2010; 116(3):354-365)
Author(s): Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2010
Volume: 116
Issue: 3
Pages: 354-365
Print publication date: 01/07/2010
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
URL: http://dx.doi.org/10.1182/blood-2009-11-254441
DOI: 10.1182/blood-2009-11-254441
Notes: Presented in part at the XXIV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases (IACRLRD), Columbus, OH, October 15-16, 2009.
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