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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

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
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
Pre-treatment cytogenetics is a known predictor of outcome in haematological malignancies. However, its usefulness in adult acute lymphoblastic leukaemia is generally limited to the presence of the Philadelphia chromosome (Ph); because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1,522 adult patients enrolled on the MRC UKALLXII / ECOG 2993 trial. The incidence and clinical associations for over 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21;q23), t(8;14)(q24.1;q32), complex karyotype (five or more chromosomal abnormalities) or low hypodiploidy / near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared to 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 gender, 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 can and should be used to risk stratify adults with ALL in future trials.
0006-4971
3189-3197
Moorman, Anthony V.
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Harrison, Christine J.
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Buck, Georgina A.N.
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Richards, Sue M.
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Secker-Walker, Lorna M.
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Martineau, Mary
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Vance, Gail H.
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Cherry, Athena M.
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Higgins, Rodney R.
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Fielding, Adele K.
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Foroni, Letizia
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Paietta, Elisabeth
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Tallman, Martin S.
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Litzow, Mark R.
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Wiernik, Peter H.
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Rowe, Jacob M.
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Goldstone, Anthony H.
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Dewald, Gordon W.
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Medical Research Council (MRC)/National Cancer Research Institute (NCRI)
Moorman, Anthony V.
e4ced178-ee03-47ef-bc5e-25d8453951d5
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Buck, Georgina A.N.
e9d417bd-2c32-4d95-8a41-3a42e275d9f3
Richards, Sue M.
d3a46ce3-0633-4781-812e-fa9faa77cad5
Secker-Walker, Lorna M.
337494d0-662a-4abb-8226-bdc045b04384
Martineau, Mary
6cc6f57f-7b57-4583-81eb-17dac737e35c
Vance, Gail H.
cce0e343-cbbb-4458-b501-58616a56b498
Cherry, Athena M.
dee16872-dd72-471c-a2e3-b331f4e210f5
Higgins, Rodney R.
c4b86b85-7cfb-4152-8e8d-76af72e6db24
Fielding, Adele K.
f1a331a0-d040-4dae-84ca-5234cc0f9375
Foroni, Letizia
eba61549-49cb-4d42-8be9-dd39167c5f1f
Paietta, Elisabeth
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Tallman, Martin S.
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Litzow, Mark R.
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Wiernik, Peter H.
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Rowe, Jacob M.
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Goldstone, Anthony H.
8ce52bfc-d857-4592-97a3-79525672b39d
Dewald, Gordon W.
0d096653-a2d5-4357-bc59-f5e110ba00e5

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, Tallman, Martin S., Litzow, Mark R., Wiernik, Peter H., Rowe, Jacob M., Goldstone, Anthony H. and Dewald, Gordon W. , Medical Research Council (MRC)/National Cancer Research Institute (NCRI) (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, 109 (8), 3189-3197. (doi:10.1182/blood-2006-10-051912).

Record type: Article

Abstract

Pre-treatment cytogenetics is a known predictor of outcome in haematological malignancies. However, its usefulness in adult acute lymphoblastic leukaemia is generally limited to the presence of the Philadelphia chromosome (Ph); because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1,522 adult patients enrolled on the MRC UKALLXII / ECOG 2993 trial. The incidence and clinical associations for over 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21;q23), t(8;14)(q24.1;q32), complex karyotype (five or more chromosomal abnormalities) or low hypodiploidy / near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared to 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 gender, 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 can and should be used to risk stratify adults with ALL in future trials.

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Published date: 15 April 2007
Additional Information: Blood First Edition Paper, prepublished online December 14, 2006

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Local EPrints ID: 44337
URI: http://eprints.soton.ac.uk/id/eprint/44337
ISSN: 0006-4971
PURE UUID: dc1a76e6-8ff5-4dad-a8c0-04ab1a0ad6c5

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Date deposited: 27 Feb 2007
Last modified: 15 Mar 2024 09:03

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Contributors

Author: Anthony V. Moorman
Author: Christine J. Harrison
Author: Georgina A.N. Buck
Author: Sue M. Richards
Author: Lorna M. Secker-Walker
Author: Mary Martineau
Author: Gail H. Vance
Author: Athena M. Cherry
Author: Rodney R. Higgins
Author: Adele K. Fielding
Author: Letizia Foroni
Author: Elisabeth Paietta
Author: Martin S. Tallman
Author: Mark R. Litzow
Author: Peter H. Wiernik
Author: Jacob M. Rowe
Author: Anthony H. Goldstone
Author: Gordon W. Dewald
Corporate Author: Medical Research Council (MRC)/National Cancer Research Institute (NCRI)

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