Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia: Results from Four ECOG-ACRIN Prospective Therapeutic Trials

on behalf of the ECOG-ACRIN Cancer Research Group

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Abstract

The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML.

Original languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalLeukemia Research
Volume59
DOIs
StatePublished - Aug 1 2017

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Monosomy
Karyotype
Acute Myeloid Leukemia
Survival
Therapeutics

Keywords

  • Complex Karyotype
  • Cytogenetics
  • Monosomal Karyotype
  • Monosomy 17
  • Monosomy 5
  • Monosomy 7
  • Myeloid Leukemia
  • Prognosis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

@article{592582f13c4240c7ad7608c4bba3edca,
title = "Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia: Results from Four ECOG-ACRIN Prospective Therapeutic Trials",
abstract = "The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93{\%}) were MK+/CK+ with 87{\%} (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93{\%}; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43{\%} (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML.",
keywords = "Complex Karyotype, Cytogenetics, Monosomal Karyotype, Monosomy 17, Monosomy 5, Monosomy 7, Myeloid Leukemia, Prognosis",
author = "{on behalf of the ECOG-ACRIN Cancer Research Group} and Strickland, {Stephen A.} and Zhuoxin Sun and Ketterling, {Rhett P.} and Cherry, {Athena M.} and Cripe, {Larry D.} and Gordon Dewald and Fernandez, {Hugo F.} and Hicks, {Gary A.} and Higgins, {Rodney R.} and Lazarus, {Hillard M.} and Litzow, {Mark R.} and Luger, {Selina M.} and Paietta, {Elisabeth M.} and Rowe, {Jacob M.} and Vance, {Gail H.} and Peter Wiernik and Wiktor, {Anne E.} and Yanming Zhang and Tallman, {Martin S.}",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.leukres.2017.05.010",
language = "English (US)",
volume = "59",
pages = "55--64",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia

T2 - Results from Four ECOG-ACRIN Prospective Therapeutic Trials

AU - on behalf of the ECOG-ACRIN Cancer Research Group

AU - Strickland, Stephen A.

AU - Sun, Zhuoxin

AU - Ketterling, Rhett P.

AU - Cherry, Athena M.

AU - Cripe, Larry D.

AU - Dewald, Gordon

AU - Fernandez, Hugo F.

AU - Hicks, Gary A.

AU - Higgins, Rodney R.

AU - Lazarus, Hillard M.

AU - Litzow, Mark R.

AU - Luger, Selina M.

AU - Paietta, Elisabeth M.

AU - Rowe, Jacob M.

AU - Vance, Gail H.

AU - Wiernik, Peter

AU - Wiktor, Anne E.

AU - Zhang, Yanming

AU - Tallman, Martin S.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML.

AB - The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML.

KW - Complex Karyotype

KW - Cytogenetics

KW - Monosomal Karyotype

KW - Monosomy 17

KW - Monosomy 5

KW - Monosomy 7

KW - Myeloid Leukemia

KW - Prognosis

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UR - http://www.scopus.com/inward/citedby.url?scp=85019731319&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2017.05.010

DO - 10.1016/j.leukres.2017.05.010

M3 - Article

C2 - 28551161

AN - SCOPUS:85019731319

VL - 59

SP - 55

EP - 64

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

ER -