TY - JOUR
T1 - Refinement of cytogenetic classification in acute myeloid leukemia
T2 - determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials
AU - Grimwade, David
AU - Hills, Robert K
AU - Moorman, Anthony V
AU - Walker, Helen
AU - Chatters, Stephen
AU - Goldstone, Anthony H
AU - Wheatley, Keith
AU - Harrison, Christine J
AU - Burnett, Alan K
AU - National Cancer Research Institute Adult Leukaemia Working Group
AU - Johnsen, Hans Erik
PY - 2010/7/22
Y1 - 2010/7/22
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Bone Marrow Transplantation
KW - Chromosome Aberrations
KW - Chromosomes, Human, Pair 15
KW - Chromosomes, Human, Pair 17
KW - Cohort Studies
KW - Cytogenetic Analysis
KW - Female
KW - Great Britain
KW - Humans
KW - Karyotyping
KW - Leukemia, Myeloid, Acute
KW - Male
KW - Middle Aged
KW - Multivariate Analysis
KW - Mutation
KW - Nuclear Proteins
KW - Prognosis
KW - Risk Factors
KW - Survival Analysis
KW - Translocation, Genetic
KW - Treatment Outcome
KW - Young Adult
KW - fms-Like Tyrosine Kinase 3
U2 - 10.1182/blood-2009-11-254441
DO - 10.1182/blood-2009-11-254441
M3 - Journal article
C2 - 20385793
SN - 0006-4971
VL - 116
SP - 354
EP - 365
JO - Blood
JF - Blood
IS - 3
ER -