Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance

Analysis of patients in ECOG-ACRIN cancer research group trials, 1980-2008

Chezi Ganzel, Judith Manola, Dan Douer, Jacob M. Rowe, Hugo F. Fernandez, Elisabeth M. Paietta, Mark R. Litzow, Ju Whei Lee, Selina M. Luger, Hillard M. Lazarus, Larry D. Cripe, Martin S. Tallman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods: Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results: Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD (P = .005), skin involvement (P = .002), spleen (P < .001), and liver (P < .001), but not CNS (P = .34), nodal involvement (P = .94), and gingival hypertrophy (P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion: This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.

Original languageEnglish (US)
Pages (from-to)3544-3553
Number of pages10
JournalJournal of Clinical Oncology
Volume34
Issue number29
DOIs
StatePublished - Oct 10 2016

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Acute Myeloid Leukemia
Research
Neoplasms
Gingival Hypertrophy
Spleen
Clinical Trials
Skin
Acute Promyelocytic Leukemia
Survival
Liver
Incidence
Gingiva
Cytogenetics
Physical Examination
Lymph Nodes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance : Analysis of patients in ECOG-ACRIN cancer research group trials, 1980-2008. / Ganzel, Chezi; Manola, Judith; Douer, Dan; Rowe, Jacob M.; Fernandez, Hugo F.; Paietta, Elisabeth M.; Litzow, Mark R.; Lee, Ju Whei; Luger, Selina M.; Lazarus, Hillard M.; Cripe, Larry D.; Tallman, Martin S.

In: Journal of Clinical Oncology, Vol. 34, No. 29, 10.10.2016, p. 3544-3553.

Research output: Contribution to journalArticle

Ganzel, Chezi ; Manola, Judith ; Douer, Dan ; Rowe, Jacob M. ; Fernandez, Hugo F. ; Paietta, Elisabeth M. ; Litzow, Mark R. ; Lee, Ju Whei ; Luger, Selina M. ; Lazarus, Hillard M. ; Cripe, Larry D. ; Tallman, Martin S. / Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance : Analysis of patients in ECOG-ACRIN cancer research group trials, 1980-2008. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 29. pp. 3544-3553.
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abstract = "Purpose: Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods: Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results: Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7{\%}. The sites involved were: lymph nodes (11.5{\%}), spleen (7.3{\%}), liver (5.3{\%}), skin (4.5{\%}), gingiva (4.4{\%}), and CNS (1.1{\%}). Most patients (65.3{\%}) had only one site of EMD, 20.9{\%} had two sites, 9.5{\%} had three sites, and 3.4{\%} had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD (P = .005), skin involvement (P = .002), spleen (P < .001), and liver (P < .001), but not CNS (P = .34), nodal involvement (P = .94), and gingival hypertrophy (P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion: This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.",
author = "Chezi Ganzel and Judith Manola and Dan Douer and Rowe, {Jacob M.} and Fernandez, {Hugo F.} and Paietta, {Elisabeth M.} and Litzow, {Mark R.} and Lee, {Ju Whei} and Luger, {Selina M.} and Lazarus, {Hillard M.} and Cripe, {Larry D.} and Tallman, {Martin S.}",
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T1 - Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance

T2 - Analysis of patients in ECOG-ACRIN cancer research group trials, 1980-2008

AU - Ganzel, Chezi

AU - Manola, Judith

AU - Douer, Dan

AU - Rowe, Jacob M.

AU - Fernandez, Hugo F.

AU - Paietta, Elisabeth M.

AU - Litzow, Mark R.

AU - Lee, Ju Whei

AU - Luger, Selina M.

AU - Lazarus, Hillard M.

AU - Cripe, Larry D.

AU - Tallman, Martin S.

PY - 2016/10/10

Y1 - 2016/10/10

N2 - Purpose: Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods: Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results: Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD (P = .005), skin involvement (P = .002), spleen (P < .001), and liver (P < .001), but not CNS (P = .34), nodal involvement (P = .94), and gingival hypertrophy (P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion: This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.

AB - Purpose: Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods: Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results: Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD (P = .005), skin involvement (P = .002), spleen (P < .001), and liver (P < .001), but not CNS (P = .34), nodal involvement (P = .94), and gingival hypertrophy (P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion: This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.

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