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


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.
Department of Haematology, Herlev University Hospital, Copenhagen, Denmark.
Marianne Hutchings
MH
Hoffmann
Tobias Wirenfeldt
TW
Klausen
Martin
M
Boegsted
Steffen Falgreen
SF
Larsen
Alexander
A
Schmitz
Eva Birgitte
EB
Leinoe
Kjeld
K
Schmiegelow
Henrik
H
Hasle
Olav Jonas
OJ
Bergmann
Suzette
S
Sorensen
Mette
M
Nyegaard
Karen
K
Dybkaer
Hans Erik
HE
Johnsen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D001856:Bone Marrow Examination; D018968:CD58 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D055815:Young Adult
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D018968:CD58 Antigens; D018950:Lipopolysaccharide Receptors; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens