Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia

A Southwest oncology group/Eastern cooperative oncology group study

Marilyn L. Slovak, Kenneth J. Kopecky, Peter A. Cassileth, David H. Harrington, Karl S. Theil, Anwar Mohamed, Elisabeth M. Paietta, Cheryl L. Willman, David R. Head, Jacob M. Rowe, Stephen J. Forman, Frederick R. Appelbaum

Research output: Contribution to journalArticle

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Abstract

The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P < .0001) among the 4 groups: favorable, 84% (95% confidence interval [CI], 77%-90%); intermediate, 76% (CI, 71%-81%); unfavorable, 55% (CI, 48%-63%); and unknown, 54% (CI, 33%-74%). There was similar significant heterogeneity of OS (P < .0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3.33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P= .0003), with significant evidence of interaction (P = .017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.

Original languageEnglish (US)
Pages (from-to)4075-4083
Number of pages9
JournalBlood
Volume96
Issue number13
StatePublished - 2000
Externally publishedYes

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Oncology
Acute Myeloid Leukemia
Cytogenetics
Confidence Intervals
Homologous Transplantation
Bone
Chemotherapy
Bone Marrow Transplantation
Therapeutics
Survival
Survival Rate
Drug Therapy
Autologous Transplantation
Karyotype
Cause of Death
Leukemia
Multivariate Analysis
Tissue Donors
Clinical Trials
Databases

ASJC Scopus subject areas

  • Hematology

Cite this

Slovak, M. L., Kopecky, K. J., Cassileth, P. A., Harrington, D. H., Theil, K. S., Mohamed, A., ... Appelbaum, F. R. (2000). Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: A Southwest oncology group/Eastern cooperative oncology group study. Blood, 96(13), 4075-4083.

Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia : A Southwest oncology group/Eastern cooperative oncology group study. / Slovak, Marilyn L.; Kopecky, Kenneth J.; Cassileth, Peter A.; Harrington, David H.; Theil, Karl S.; Mohamed, Anwar; Paietta, Elisabeth M.; Willman, Cheryl L.; Head, David R.; Rowe, Jacob M.; Forman, Stephen J.; Appelbaum, Frederick R.

In: Blood, Vol. 96, No. 13, 2000, p. 4075-4083.

Research output: Contribution to journalArticle

Slovak, ML, Kopecky, KJ, Cassileth, PA, Harrington, DH, Theil, KS, Mohamed, A, Paietta, EM, Willman, CL, Head, DR, Rowe, JM, Forman, SJ & Appelbaum, FR 2000, 'Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: A Southwest oncology group/Eastern cooperative oncology group study', Blood, vol. 96, no. 13, pp. 4075-4083.
Slovak, Marilyn L. ; Kopecky, Kenneth J. ; Cassileth, Peter A. ; Harrington, David H. ; Theil, Karl S. ; Mohamed, Anwar ; Paietta, Elisabeth M. ; Willman, Cheryl L. ; Head, David R. ; Rowe, Jacob M. ; Forman, Stephen J. ; Appelbaum, Frederick R. / Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia : A Southwest oncology group/Eastern cooperative oncology group study. In: Blood. 2000 ; Vol. 96, No. 13. pp. 4075-4083.
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abstract = "The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P < .0001) among the 4 groups: favorable, 84{\%} (95{\%} confidence interval [CI], 77{\%}-90{\%}); intermediate, 76{\%} (CI, 71{\%}-81{\%}); unfavorable, 55{\%} (CI, 48{\%}-63{\%}); and unknown, 54{\%} (CI, 33{\%}-74{\%}). There was similar significant heterogeneity of OS (P < .0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3.33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P= .0003), with significant evidence of interaction (P = .017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.",
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T1 - Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia

T2 - A Southwest oncology group/Eastern cooperative oncology group study

AU - Slovak, Marilyn L.

AU - Kopecky, Kenneth J.

AU - Cassileth, Peter A.

AU - Harrington, David H.

AU - Theil, Karl S.

AU - Mohamed, Anwar

AU - Paietta, Elisabeth M.

AU - Willman, Cheryl L.

AU - Head, David R.

AU - Rowe, Jacob M.

AU - Forman, Stephen J.

AU - Appelbaum, Frederick R.

PY - 2000

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