Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial

Anthony V. Moorman, Christine J. Harrison, Georgina A N Buck, Sue M. Richards, Lorna M. Secker-Walker, Mary Martineau, Gail H. Vance, Athena M. Cherry, Rodney R. Higgins, Adele K. Fielding, Letizia Foroni, Elisabeth M. Paietta, Martin S. Tallman, Mark R. Litzow, Peter H. Wiernik, Jacob M. Rowe, Anthony H. Goldstone, Gordon W. Dewald

Research output: Contribution to journalArticle

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Abstract

Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. The incidence and clinical associations for more than 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21; q23), t(8;14)(q24.1;q32), complex karyotype (5 or more chromosomal abnormalities), or low hypodiploidy/near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared with other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype, and Ho-Tr was independent of sex, age, white cell count, and T-cell status among Ph-negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph chromosome can and should be used to risk stratify adults with ALL in future trials.

Original languageEnglish (US)
Pages (from-to)3189-3197
Number of pages9
JournalBlood
Volume109
Issue number8
DOIs
StatePublished - Apr 15 2007
Externally publishedYes

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Oncology
Cytogenetic Analysis
Chromosomes
Karyotype
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Biomedical Research
Triploidy
Philadelphia Chromosome
Cytogenetics
T-cells
Chromosome Aberrations
Chromosomes, Human, Pair 4
Polyploidy
Incidence
Hematologic Neoplasms
Treatment Failure
Disease-Free Survival
Multivariate Analysis
Cell Count
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL) : Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. / Moorman, Anthony V.; Harrison, Christine J.; Buck, Georgina A N; Richards, Sue M.; Secker-Walker, Lorna M.; Martineau, Mary; Vance, Gail H.; Cherry, Athena M.; Higgins, Rodney R.; Fielding, Adele K.; Foroni, Letizia; Paietta, Elisabeth M.; Tallman, Martin S.; Litzow, Mark R.; Wiernik, Peter H.; Rowe, Jacob M.; Goldstone, Anthony H.; Dewald, Gordon W.

In: Blood, Vol. 109, No. 8, 15.04.2007, p. 3189-3197.

Research output: Contribution to journalArticle

Moorman, AV, Harrison, CJ, Buck, GAN, Richards, SM, Secker-Walker, LM, Martineau, M, Vance, GH, Cherry, AM, Higgins, RR, Fielding, AK, Foroni, L, Paietta, EM, Tallman, MS, Litzow, MR, Wiernik, PH, Rowe, JM, Goldstone, AH & Dewald, GW 2007, 'Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial', Blood, vol. 109, no. 8, pp. 3189-3197. https://doi.org/10.1182/blood-2006-10-051912
Moorman, Anthony V. ; Harrison, Christine J. ; Buck, Georgina A N ; Richards, Sue M. ; Secker-Walker, Lorna M. ; Martineau, Mary ; Vance, Gail H. ; Cherry, Athena M. ; Higgins, Rodney R. ; Fielding, Adele K. ; Foroni, Letizia ; Paietta, Elisabeth M. ; Tallman, Martin S. ; Litzow, Mark R. ; Wiernik, Peter H. ; Rowe, Jacob M. ; Goldstone, Anthony H. ; Dewald, Gordon W. / Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL) : Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. In: Blood. 2007 ; Vol. 109, No. 8. pp. 3189-3197.
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abstract = "Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. The incidence and clinical associations for more than 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21; q23), t(8;14)(q24.1;q32), complex karyotype (5 or more chromosomal abnormalities), or low hypodiploidy/near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared with other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype, and Ho-Tr was independent of sex, age, white cell count, and T-cell status among Ph-negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph chromosome can and should be used to risk stratify adults with ALL in future trials.",
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T1 - Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL)

T2 - Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial

AU - Moorman, Anthony V.

AU - Harrison, Christine J.

AU - Buck, Georgina A N

AU - Richards, Sue M.

AU - Secker-Walker, Lorna M.

AU - Martineau, Mary

AU - Vance, Gail H.

AU - Cherry, Athena M.

AU - Higgins, Rodney R.

AU - Fielding, Adele K.

AU - Foroni, Letizia

AU - Paietta, Elisabeth M.

AU - Tallman, Martin S.

AU - Litzow, Mark R.

AU - Wiernik, Peter H.

AU - Rowe, Jacob M.

AU - Goldstone, Anthony H.

AU - Dewald, Gordon W.

PY - 2007/4/15

Y1 - 2007/4/15

N2 - Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. The incidence and clinical associations for more than 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21; q23), t(8;14)(q24.1;q32), complex karyotype (5 or more chromosomal abnormalities), or low hypodiploidy/near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared with other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype, and Ho-Tr was independent of sex, age, white cell count, and T-cell status among Ph-negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph chromosome can and should be used to risk stratify adults with ALL in future trials.

AB - Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. The incidence and clinical associations for more than 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21; q23), t(8;14)(q24.1;q32), complex karyotype (5 or more chromosomal abnormalities), or low hypodiploidy/near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared with other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype, and Ho-Tr was independent of sex, age, white cell count, and T-cell status among Ph-negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph chromosome can and should be used to risk stratify adults with ALL in future trials.

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