title: Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment.
abstract: Myelodysplastic syndromes (MDS) are a group of clonal disorders of the bone marrow characterized by peripheral cytopenias. Standard treatment in low- and intermediate-I-risk MDS is supportive therapy consisting of regular transfusions and growth factors, that is, erythropoietin (Epo) and granulocyte-colony-stimulating factor (G-CSF). Because flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry (FCM) was instrumental in predicting response. In 46 patients with low- and intermediate-I-risk MDS that were treated with Epo/G-CSF, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloblasts identified nonresponders among patients with the greatest response probability according to the predictive model of Hellström-Lindberg et al. Moreover, aberrant FCM of myeloblasts acted as a significant biomarker for treatment failure in multivariate analysis. A new predictive model based on the basis FCM combined with previously validated Epo levels is proposed defining 3 subgroups with 94%, 17%, and 11% response probability. In conclusion, FCM may add significantly to well-known predictive parameters in selecting MDS patients eligible for Epo/G-CSF treatment. This is of relevance regarding prevention of treatment failure.
authors.affiliation: Department of Hematology, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands.
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.forename: Canan
authors.initials: C
authors.lastname: Alhan
authors.forename: Martine E D
authors.initials: ME
authors.lastname: Chamuleau
authors.forename: Maurice J D L
authors.initials: MJ
authors.lastname: van der Vorst
authors.forename: Corien
authors.initials: C
authors.lastname: Eeltink
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D004921:Erythropoietin / Q000097:blood / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor