Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes

Abstract

Prolonged thrombocytopenia is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, its pathogenesis has remained obscure. In the present study, we used flow cytometry to determine the frequency of bone marrow megakaryocytes (MKs) and MK ploidy distributions in allo-HSCT recipients with or without prolonged thrombocytopenia (n = 32 and 27, respectively) and healthy volunteers (n = 13). In addition, the expression of c-Mpl in MKs was measured. The results indicate that the proportions of MKs in marrow mononuclear cells or the percentages of CD110(+) MKs in total MKs did not significantly differ between the 3 groups; however, in a comparison of nonthrombocytopenic allo-HSCT recipients to healthy volunteers, the allo-HSCT patients who had prolonged thrombocytopenia exhibited significant shifts toward low ploidy cells (left shift), which were accompanied by a marked increase in ≤ 8N cells (P = .036 and P < .001, respectively) and significant decreases in 16N cells (P < .001 and P < .001, respectively) and ≥ 32N cells (P = .01 and P <.001, respectively). These results indicate that there were more immature MKs in allo-HSCT recipients who had prolonged thrombocytopenia, in comparison to nonthrombocytopenic allo-HSCT recipients and healthy volunteers. We conclude that prolonged thrombocytopenia and slow platelet engraftment after allo-HSCT may be related to a reduction in ploidy and an immaturation of MKs.