Thrombocytopenia is a critical complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its pathogenesis has remained obscure. Thrombopoietin (TPO) has been identified as a key cytokine for both megakaryogenesis and thrombopoiesis; however, the kinetics of TPO production after allo-HSCT has not been reported. This study characterized the kinetics of TPO and its correlation with the megakaryocyte ploidy distribution pattern within 60 days of allo-HSCT.
A total of 46 consecutive patients who underwent allo-HSCT from October 2008 to December 2008 were included in the study. The TPO levels and the ploidy distribution pattern of MKs were measured using ELISA and flow cytometric analysis, respectively. The results indicate that the TPO levels and the platelet counts followed opposite trends after allo-HSCT. Multivariate analysis indicate that endogenous TPO levels before allo-HSCT, and the number of transplanted CD34+ cells were significant predisposing factors for rapid platelet engraftment (P=0.010 and 0.007, respectively). Furthermore, we found a reduction of ploidy and an increase in immature MKs in patients with higher endogenous TPO levels (> 250 pg/ml) on day 60 after allo-HSCT. Moreover, lower TPO levels (≤250 pg/ml) on day 60 after allo-HSCT were associated with significantly improved 2-year OS (P=0.032) and reduced TRM (P=0.026).
Our results suggest that increased endogenous TPO levels may not be sufficient after allo-HSCT, and that the decreased ability of TPO may account for the appearance of antibodies. The use of exogenous rhTPO may promote platelet recovery after allo-HSCT. However, these possibilities need to be examined further.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.