Elevated Dosing of Recombinant Human Thrombopoietin Accelerates Platelet Engraftment in Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective, Dosage-Optimization, Controlled Clinical Study

Objective: The optimal dosage of recombinant human thrombopoietin (rhTPO) for enhancing platelet engraftment following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined. We have crafted a prospective, dose-exploration, controlled clinical study to evaluate the effectiveness and safety of escalating doses rhTPO in facilitating platelet engraftment post-transplantation.

Methods: The study encompassed 57 individuals undergoing allo-HSCT. Commencing day +1 post-transplantation, patients were administered rhTPO therapy. The experimental group, comprising 27 patients, received a continous daily dosage of 22500 U of rhTPO until platelet engraftment was achieved. While the control group, consisting of 30 participants, was given a continuous daily dosage of 15000 U of rhTPO，also until platelet engraftment occurred.

Results: Patients in the experimental group, who received 22,500 U/day rhTPO, achieved a significantly earlier median time to platelet engraftment compared to the control group (12 vs. 13 days, P=0.042, z=4.142) and reached platelet counts of ≥30×10⁹/L more rapidly (13 vs. 16 days, z=3.936, P=0.047). There was a noticeable trend in the experimental group towards earlier attainment of higher platelet thresholds of 50×10⁹/L, 75×10⁹/L, and 100×10⁹/L (15 vs. 20 days, 18 vs. 22 days, 22.5 vs. 28 days). No instances of delayed platelet engraftment were noted in either group. By day 21, the cumulative platelet engraftment rate stood at 96.3% for the experimental group and 83.3% for the control group. By day 60, both groups had achieved a full 100% engraftment rate. Additionally, the experimental group experienced an earlier median time to neutrophil engraftment (11 vs. 12.5 days, z=4.534, P=0.033). During the follow-up period, both groups showed a 100% one-year overall survival rate. The one-year relapse-free survival rates were 96.3% for the experimental group and 93.3% for the control group, indicating no significant disparity. Notably, the cumulative incidence of moderate to severe acute graft-versus-host disease (aGVHD) was significantly lower in the experimental group (14.8% vs. 40.0%, P=0.043). Safety assessments, encompassing evaluations of adverse events such as thrombosis and bleeding, confirmed that the higher dosage of rhTPO was both safe and reliable.

Conclusion: Escalating the dosage of rhTPO injections demonstrates a safe and efficacious approach to enhancing platelet engraftment in patients following allo-HSCT. This strategy not only accelerates the recovery of platelet levels but also contributes to the overall therapeutic regimen without compromising patient safety.