Recombinant human thrombopoietin reduces the risk of acute graft-versus-host-disease and its mechanism.

Objective: Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of recombinant human thrombopoietin (rhTPO) on aGVHD using retrospective clinical data and a xenogeneic GVHD mouse model.

Methods: We retrospectively analyzed 162 patients who underwent allo-HSCT between 2016 and 2018, comparing outcomes between those treated with rhTPO and those who were not. Additionally, a murine GVHD model was established using irradiated Balb/c mice that received allogeneic PBMCs. Mice were treated with different doses of rhTPO to assess organ pathology, immune cell subsets, and cytokine expression. PBMCs from humans were also treated with rhTPO to assess proliferation and differentiation in vitro. Results were presented as odds ratios (OR) with 95 % confidence intervals (CI), and statistical significance was set at P < 0.05. P > 0.05 was considered statistically significant. All experiments were repeated for 3 times.

Results: Clinical analysis showed that rhTPO use and older patient age were independently associated with a lower incidence of aGVHD (P = 0.007 and P = 0.014, respectively). In the xenogeneic mouse model, rhTPO mitigated tissue pathology and modulated immune cell subsets. In vitro, rhTPO regulated PBMC proliferation and enhanced lymphocyte differentiation.

Conclusions: rhTPO may reduce the risk of aGVHD by modulating immune responses and protecting tissues, supporting its potential role as an adjunct therapy in allo-HSCT.