Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment

Myelodysplastic syndromes (MDS) are a group of clonal disorders of the bone marrow characterized by peripheral cytopenias. Standard treatment in low and intermediate risk-I MDS is supportive therapy consisting of regular transfusions and growth factors, i.e. erythropoietin (Epo) and G-CSF. Since 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 to a standardized Epo/G-CSF regimen. In forty-six 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 non-responders among patients with highest response probability according to the predictive model of Hellstrom-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 FCM combined with previously validated Epo levels is proposed defining three 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 and favoring the choice for alternative therapies.