Absence of aberrant myeloid progenitors by flow cytometry is associated with favorable response to azacitidine in higher risk myelodysplastic syndromes.
BACKGROUND
In intermediate-2 (Int-2) and high risk patients with myelodysplastic syndromes (MDS), treatment with azacitidine is associated with hematological improvement and prolonged overall survival (OS) in patients who respond to therapy. However, only half of the patients who are treated will benefit from this treatment. It is a major challenge to predict which patients are likely to respond to treatment. The aim of this study was to investigate the predictive value of immunophenotyping for response to treatment with azacitidine of Int-2 and high risk MDS patients.


METHODS
Bone marrow aspirates were analyzed by flow cytometry in 42 patients with Int-2 and high risk MDS, chronic myelomonocytic leukemia, or low blast count acute myeloid leukemia before treatment and after every third cycle of azacitidine. A flow score was calculated using the flow cytometric scoring system (FCSS).


RESULTS
The presence of myeloid progenitors with an aberrant immunophenotype was significantly associated with lack of response (p = 0.02). A low pretreatment FCSS was associated with significantly better OS compared with a high pretreatment FCSS (p = 0.03). A significant decrease in FCSS was observed in patients with complete response after three cycles azacitidine compared to patients with progressive disease (p = 0.006).


CONCLUSIONS
Absence of aberrant myeloid progenitor cells at baseline and/or a decrease in the FCSS during treatment identified Int-2 and high risk MDS patients who are likely to respond to treatment with azacitidine.
Department of Hematology, VU Institute of Cancer and Immunology (V-ICI), Cancer Center Amsterdam (CCA), VU University Medical Center, Amsterdam, Netherlands.
Canan
C
Alhan
Theresia M
TM
Westers
Lieke H
LH
van der Helm
Corien
C
Eeltink
Gerwin
G
Huls
Birgit I
BI
Witte
Francesca
F
Buchi
Valeria
V
Santini
Gert J
GJ
Ossenkoppele
Arjan A
AA
van de Loosdrecht
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D001854:Bone Marrow Cells / Q000145:classification / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D023461:Myeloid Progenitor Cells / Q000145:classification / Q000276:immunology / Q000473:pathology*; D011379:Prognosis; D012107:Research Design; D012189:Retrospective Studies; D012307:Risk Factors
D000964:Antimetabolites, Antineoplastic; D054316:Biomarkers, Pharmacological; D001374:Azacitidine
azacitidine; flow cytometry; myelodysplastic syndromes; response prediction