In vitro effect of eltrombopag alone and in combination with azacitidine on megakaryopoiesis in patients with myelodysplastic syndrome

In vitro effect of eltrombopag alone and in combination with azacitidine on megakaryopoiesis in patients with myelodysplastic syndrome

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Thrombocytopenia is a severe complication for patients with myelodysplastic syndrome (MDS).Eltrombopag increases platelet count in MDS patients but its combination with azacitidine elicited controversial results.We aimed to quantify the colony forming units of megakaryocytes (CFU-Mk) obtained from CD34+ bone marrow cells isolated from patients with vegemite pop art MDS and from healthy donors that were cultured in vitro in the presence or absence of azacitidine and with or without the sequential addition of eltrombopag to the culture medium.CD34+ bone marrow cells from 6 MDS patients and 3 controls were expanded in vitro and cultured for 3 days with or without azacitidine.Subsequently, a CFU-Mk assay was performed in presence or absence of eltrombopag.

The addition of eltrombopag in the CFU-Mk assay after mock treatment of CD34+ cells increased the number modular pillow stack of CFU-Mk in both controls and patients.On the contrary, using azacitidine pretreated CD34+ cells, eltrombopag minimally increased CFU-Mk in controls and produced heterogeneous response in MDS patients with no change in two patients and CFU-Mk increase in four patients.In vitro CFU-Mk assay suggest that some MDS patients are likely to benefit from the sequential addition of eltrombopag after azacitidine treatment, in the context of a personalized medicine.