Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia

Results from Cancer and Leukemia Group B 8461

Sherif Farag, Kellie J. Archer, Krzysztof Mrózek, Amy S. Ruppert, Andrew J. Carroll, James W. Vardiman, Mark J. Pettenati, Maria R. Baer, Mazin B. Qumsiyeh, Prasad R. Koduru, Yi Ning, Robert J. Mayer, Richard M. Stone, Richard A. Larson, Clara D. Bloomfield

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Abstract

We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex ≥ 3) and a group including "rare aberrations" predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex ≥ 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex ≥ 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex ≥ 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P <.001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex ≥ 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care.

Original languageEnglish (US)
Pages (from-to)63-73
Number of pages11
JournalBlood
Volume108
Issue number1
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

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Aberrations
Acute Myeloid Leukemia
Cytogenetics
Leukemia
Blood
Core Binding Factors
Neoplasms
Survival Analysis
Karyotype
Leukocyte Count
Cells
Investigational Therapies
Survival
Disease-Free Survival
Age Groups
Bone Marrow
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia : Results from Cancer and Leukemia Group B 8461. / Farag, Sherif; Archer, Kellie J.; Mrózek, Krzysztof; Ruppert, Amy S.; Carroll, Andrew J.; Vardiman, James W.; Pettenati, Mark J.; Baer, Maria R.; Qumsiyeh, Mazin B.; Koduru, Prasad R.; Ning, Yi; Mayer, Robert J.; Stone, Richard M.; Larson, Richard A.; Bloomfield, Clara D.

In: Blood, Vol. 108, No. 1, 01.07.2006, p. 63-73.

Research output: Contribution to journalArticle

Farag, S, Archer, KJ, Mrózek, K, Ruppert, AS, Carroll, AJ, Vardiman, JW, Pettenati, MJ, Baer, MR, Qumsiyeh, MB, Koduru, PR, Ning, Y, Mayer, RJ, Stone, RM, Larson, RA & Bloomfield, CD 2006, 'Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: Results from Cancer and Leukemia Group B 8461', Blood, vol. 108, no. 1, pp. 63-73. https://doi.org/10.1182/blood-2005-11-4354
Farag, Sherif ; Archer, Kellie J. ; Mrózek, Krzysztof ; Ruppert, Amy S. ; Carroll, Andrew J. ; Vardiman, James W. ; Pettenati, Mark J. ; Baer, Maria R. ; Qumsiyeh, Mazin B. ; Koduru, Prasad R. ; Ning, Yi ; Mayer, Robert J. ; Stone, Richard M. ; Larson, Richard A. ; Bloomfield, Clara D. / Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia : Results from Cancer and Leukemia Group B 8461. In: Blood. 2006 ; Vol. 108, No. 1. pp. 63-73.
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abstract = "We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5{\%} achieved complete remission (CR); 6.6{\%} survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex ≥ 3) and a group including {"}rare aberrations{"} predicted lower CR rates (25{\%} and 30{\%}) versus other patients (56{\%}). Compared with complex ≥ 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex ≥ 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex ≥ 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P <.001), with 5-year survivals of 0{\%}, 0{\%}, and 19.4{\%}, respectively, and 7.5{\%} for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex ≥ 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care.",
author = "Sherif Farag and Archer, {Kellie J.} and Krzysztof Mr{\'o}zek and Ruppert, {Amy S.} and Carroll, {Andrew J.} and Vardiman, {James W.} and Pettenati, {Mark J.} and Baer, {Maria R.} and Qumsiyeh, {Mazin B.} and Koduru, {Prasad R.} and Yi Ning and Mayer, {Robert J.} and Stone, {Richard M.} and Larson, {Richard A.} and Bloomfield, {Clara D.}",
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T1 - Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia

T2 - Results from Cancer and Leukemia Group B 8461

AU - Farag, Sherif

AU - Archer, Kellie J.

AU - Mrózek, Krzysztof

AU - Ruppert, Amy S.

AU - Carroll, Andrew J.

AU - Vardiman, James W.

AU - Pettenati, Mark J.

AU - Baer, Maria R.

AU - Qumsiyeh, Mazin B.

AU - Koduru, Prasad R.

AU - Ning, Yi

AU - Mayer, Robert J.

AU - Stone, Richard M.

AU - Larson, Richard A.

AU - Bloomfield, Clara D.

PY - 2006/7/1

Y1 - 2006/7/1

N2 - We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex ≥ 3) and a group including "rare aberrations" predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex ≥ 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex ≥ 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex ≥ 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P <.001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex ≥ 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care.

AB - We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex ≥ 3) and a group including "rare aberrations" predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex ≥ 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex ≥ 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex ≥ 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P <.001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex ≥ 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care.

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