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Vol. 42. Issue S2.
Pages 8-9 (November 2020)
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Vol. 42. Issue S2.
Pages 8-9 (November 2020)
13
DOI: 10.1016/j.htct.2020.10.014
Open Access
IN VIVO EFFECTS OF ELTROMBOPAG ON THE EXPANSION OF HEMATOPOIETIC STEM AND PROGENITOR CELLS IN APLASTIC ANAEMIA
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B.Q. Oliveiraa, B.A.A.S. Lemosa, L.F.B. Cattoa, M.F. Tellecheaa, P. Scheinbergb, P.S. Scheuchera, R.T. Caladoa
a Universidade de São Paulo (USP), São Paulo, SP, Brazil
b A Beneficência Portuguesa de São Paulo (BP), São Paulo, SP, Brazil
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Objectives: Evaluate the effects of eltrombopag on the expansion of hematopoietic stem and progenitor cell compartment in patients with immune aplastic anemia. Methods: Twelve patients with severe immune aplastic anemia who achieved hematologic response six months after initial treatment were invited to participate in the study. Six patients were treated with eltrombopag associated with cyclosporine and six were treated with rabbit antithymocyte globulin and cyclosporine, but treatment choice was not determined by this study. 25mL of bone-marrow aspiration was obtained from each patient for multiparametric analysis in an 8-color flow cytometry. Mononuclear cells were separated by gradient density centrifugation and CD34+ cells were purified using magnetic column beads. We used a 9-antibody panel to identify hematopoietic stem and progenitor cell subpopulations, as follows: hematopoietic stem cells (HSC), CD34+ CD38- CD45RA- CD90+ CD49f+; multipotent progenitor cells (MPP), CD34+ CD38- CD45RA- CD90- CD49f-; multilymphoid progenitor cells (MLP), CD34+ CD38+ CD45RA+ CD10+ CD7-; common myeloid progenitor cells (CMP), CD34+ CD38+ CD45RA- CD135+ CD10- CD7-; granulocyte-monocyte progenitor cells (GMP), CD34+ CD38+ CD45RA+ CD135+ CD10- CD7-; and megakaryocytic-erythroid progenitor cells (MEP), CD34+ CD38+ CD45RA- CD135- CD10- CD7-. Purified bone marrow CD34+ cells were also assessed in methylcellulose medium and colonies were counted 14 days after triplicate plating. Cell populations and colony formation assay were compared between the two groups using a two-tailed non-parametric Mann-Whitney test. Results: The number of CD34+ cells was similar, but patients treated with eltrombopag had more MPP cells compared to immunosuppressive therapy alone (p=0,026). No aberrant phenotype expansion was observed. There was no statistical difference in the number of colony-formation units between groups. Discussion: We found that the MPP population was the only one significantly expanded in patients treated with eltrombopag associated with immunosuppressive therapy. The MPPs belong to the hematopoietic stem cell compartment and preserve the capability of originating different blood cell lineages, but MPPs are more differentiated than HSCs. This fact may suggest that eltrombopag promotes the expansion of cells with some degree of differentiation, but yet with the capability of originating the three blood cell lineages. Our results also indicate that eltrombopag does not promote the expansion of aberrant phenotypes that could suggest malignant potential. Conclusion: Our results indicate that eltrombopag differentially expands hematopoietic multipotent progenitor cells in vivo in patients with immune aplastic anemia. Conflicts of interest: Rodrigo Tocantins Calado received speaker fee from Novartis Brasil S.A.

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Hematology, Transfusion and Cell Therapy

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