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Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate‐risk acute myeloid leukemia
Author(s) -
Hoffmann Marianne Hutchings,
Klausen Tobias Wirenfeldt,
Boegsted Martin,
Larsen Steffen Falgreen,
Schmitz Alexander,
Leinoe Eva Birgitte,
Schmiegelow Kjeld,
Hasle Henrik,
Bergmann Olav Jonas,
Sorensen Suzette,
Nyegaard Mette,
Dybkær Karen,
Johnsen Hans Erik
Publication year - 2012
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.20633
Subject(s) - cd117 , myeloid leukemia , leukemia , oncology , bone marrow , medicine , proportional hazards model , immunophenotyping , multivariate analysis , myeloid , prognostic variable , flow cytometry , pathology , immunology , biology , cd34 , stem cell , genetics
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. © 2012 International Clinical Cytometry Society