Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

Marianne Hutchings Hoffmann; Tobias Wirenfeldt Klausen; Martin Boegsted; Steffen Falgreen Larsen; Alexander Schmitz; Eva Birgitte Leinø; Kjeld Schmiegelow; Henrik Hasle; Olav Jonas Bergmann; Suzette Sorensen; Mette Nyegaard; Karen Dybkaer; Hans Erik Johnsen

doi:10.1002/cyto.b.20633

Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

Marianne Hutchings Hoffmann, Tobias Wirenfeldt Klausen, Martin Boegsted, Steffen Falgreen Larsen, Alexander Schmitz, Eva Birgitte Leinø, Kjeld Schmiegelow, Henrik Hasle, Olav Jonas Bergmann, Suzette Sorensen, Mette Nyegaard, Karen Dybkaer, Hans Erik Johnsen

10 Citations (Scopus)

Abstract

Background: Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact. Material and methods: Samples from de novo AML patients of all cytogenetic risk groups were collected at diagnosis and subjected to MFC based on a four-color antibody panels against 33 CD membrane markers and retrospectively analyzed for the leukemia blast expression pattern and mean fluorescence intensity. Identification of the leukemic blast cells was based on right angle light scatter (SSC) and expression of CD45 and the cellular heterogeneity identified by the presence of at least two distinct subsets by any CD marker. Results: Analysis of marrow samples from 86 patients with cytogenetic intermediate risk identified recurrent heterogeneous blast phenotypes for selected CD markers, three of which had prognostic impact with loss or gain of CD58, CD117, or CD14 expression. Multivariate Cox regression analysis of diagnostic variables identified poor prognostic factors: Age >55 years, presence of extramedullary disease, WHO performance score >2, a heterogeneous CD58, CD117, or CD14 expression on blast cells. Each variable added to a simple and clinical useful and MFC based prognostic score system associated to inferior survival in the intermediate risk group of AML patients. Conclusions: These observations support that leukemic blast heterogeneity detected by MFC has additional prognostic significance in de novo AML; however, the score system needs to be prospectively validated in future clinical trials before implementation.

Original language	English
Journal	Cytometry. Part B: Clinical Cytometry
Volume	82
Issue number	3
Pages (from-to)	123-31
Number of pages	9
ISSN	1552-4949
DOIs	https://doi.org/10.1002/cyto.b.20633
Publication status	Published - May 2012

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Hoffmann, M. H., Klausen, T. W., Boegsted, M., Larsen, S. F., Schmitz, A., Leinø, E. B., Schmiegelow, K., Hasle, H., Bergmann, O. J., Sorensen, S., Nyegaard, M., Dybkaer, K., & Johnsen, H. E. (2012). Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia. Cytometry. Part B: Clinical Cytometry, 82(3), 123-31. https://doi.org/10.1002/cyto.b.20633

Hoffmann, MH, Klausen, TW, Boegsted, M, Larsen, SF, Schmitz, A, Leinø, EB, Schmiegelow, K, Hasle, H, Bergmann, OJ, Sorensen, S, Nyegaard, M, Dybkaer, K & Johnsen, HE 2012, 'Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia', Cytometry. Part B: Clinical Cytometry, vol. 82, no. 3, pp. 123-31. https://doi.org/10.1002/cyto.b.20633

@article{3661f1ad66064c90b85be70dd4ec352d,

title = "Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia",

abstract = "Background: Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact. Material and methods: Samples from de novo AML patients of all cytogenetic risk groups were collected at diagnosis and subjected to MFC based on a four-color antibody panels against 33 CD membrane markers and retrospectively analyzed for the leukemia blast expression pattern and mean fluorescence intensity. Identification of the leukemic blast cells was based on right angle light scatter (SSC) and expression of CD45 and the cellular heterogeneity identified by the presence of at least two distinct subsets by any CD marker. Results: Analysis of marrow samples from 86 patients with cytogenetic intermediate risk identified recurrent heterogeneous blast phenotypes for selected CD markers, three of which had prognostic impact with loss or gain of CD58, CD117, or CD14 expression. Multivariate Cox regression analysis of diagnostic variables identified poor prognostic factors: Age >55 years, presence of extramedullary disease, WHO performance score >2, a heterogeneous CD58, CD117, or CD14 expression on blast cells. Each variable added to a simple and clinical useful and MFC based prognostic score system associated to inferior survival in the intermediate risk group of AML patients. Conclusions: These observations support that leukemic blast heterogeneity detected by MFC has additional prognostic significance in de novo AML; however, the score system needs to be prospectively validated in future clinical trials before implementation.",

author = "Hoffmann, {Marianne Hutchings} and Klausen, {Tobias Wirenfeldt} and Martin Boegsted and Larsen, {Steffen Falgreen} and Alexander Schmitz and Lein{\o}, {Eva Birgitte} and Kjeld Schmiegelow and Henrik Hasle and Bergmann, {Olav Jonas} and Suzette Sorensen and Mette Nyegaard and Karen Dybkaer and Johnsen, {Hans Erik}",

note = "Copyright {\textcopyright} 2012 International Clinical Cytometry Society.",

year = "2012",

month = may,

doi = "10.1002/cyto.b.20633",

language = "English",

volume = "82",

pages = "123--31",

journal = "Cytometry Part B - Clinical Cytometry",

issn = "1552-4949",

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TY - JOUR

T1 - Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

AU - Hoffmann, Marianne Hutchings

AU - Klausen, Tobias Wirenfeldt

AU - Boegsted, Martin

AU - Larsen, Steffen Falgreen

AU - Schmitz, Alexander

AU - Leinø, Eva Birgitte

AU - Schmiegelow, Kjeld

AU - Hasle, Henrik

AU - Bergmann, Olav Jonas

AU - Sorensen, Suzette

AU - Nyegaard, Mette

AU - Dybkaer, Karen

AU - Johnsen, Hans Erik

PY - 2012/5

Y1 - 2012/5

N2 - Background: Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact. Material and methods: Samples from de novo AML patients of all cytogenetic risk groups were collected at diagnosis and subjected to MFC based on a four-color antibody panels against 33 CD membrane markers and retrospectively analyzed for the leukemia blast expression pattern and mean fluorescence intensity. Identification of the leukemic blast cells was based on right angle light scatter (SSC) and expression of CD45 and the cellular heterogeneity identified by the presence of at least two distinct subsets by any CD marker. Results: Analysis of marrow samples from 86 patients with cytogenetic intermediate risk identified recurrent heterogeneous blast phenotypes for selected CD markers, three of which had prognostic impact with loss or gain of CD58, CD117, or CD14 expression. Multivariate Cox regression analysis of diagnostic variables identified poor prognostic factors: Age >55 years, presence of extramedullary disease, WHO performance score >2, a heterogeneous CD58, CD117, or CD14 expression on blast cells. Each variable added to a simple and clinical useful and MFC based prognostic score system associated to inferior survival in the intermediate risk group of AML patients. Conclusions: These observations support that leukemic blast heterogeneity detected by MFC has additional prognostic significance in de novo AML; however, the score system needs to be prospectively validated in future clinical trials before implementation.

AB - Background: Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact. Material and methods: Samples from de novo AML patients of all cytogenetic risk groups were collected at diagnosis and subjected to MFC based on a four-color antibody panels against 33 CD membrane markers and retrospectively analyzed for the leukemia blast expression pattern and mean fluorescence intensity. Identification of the leukemic blast cells was based on right angle light scatter (SSC) and expression of CD45 and the cellular heterogeneity identified by the presence of at least two distinct subsets by any CD marker. Results: Analysis of marrow samples from 86 patients with cytogenetic intermediate risk identified recurrent heterogeneous blast phenotypes for selected CD markers, three of which had prognostic impact with loss or gain of CD58, CD117, or CD14 expression. Multivariate Cox regression analysis of diagnostic variables identified poor prognostic factors: Age >55 years, presence of extramedullary disease, WHO performance score >2, a heterogeneous CD58, CD117, or CD14 expression on blast cells. Each variable added to a simple and clinical useful and MFC based prognostic score system associated to inferior survival in the intermediate risk group of AML patients. Conclusions: These observations support that leukemic blast heterogeneity detected by MFC has additional prognostic significance in de novo AML; however, the score system needs to be prospectively validated in future clinical trials before implementation.

U2 - 10.1002/cyto.b.20633

DO - 10.1002/cyto.b.20633

M3 - Journal article

C2 - 22328535

SN - 1552-4949

VL - 82

SP - 123

EP - 131

JO - Cytometry Part B - Clinical Cytometry

JF - Cytometry Part B - Clinical Cytometry

IS - 3

ER -

Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

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