Recombinant human thrombopoietin safety and efficacy in pediatric allogeneic hematopoietic stem cell transplantation: A cohort study

Abstract

Background: The safety and efficacy of recombinant human thrombopoietin (rhTPO) administered after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children (0-9 years old) and adolescents (10-17 years old) with hematological disorders remain unclear.

Aim: To evaluate the safety and efficacy of rhTPO administered before platelet (PLT) engraftment in pediatric patients with hematological disorders undergoing HSCT, and to investigate its effects on the incidence of graft-vs-host disease (GVHD) and other transplant-related outcomes.

Methods: This study enrolled 79 pediatric patients with hematological disorders who received rhTPO after allo-HSCT. The safety and tolerability of rhTPO were evaluated and compared in children (n = 36) and adolescents (n = 43) with hematological disorders. We also investigated the effects of rhTPO administration on the incidence of GVHD and other transplant-related outcomes. Additionally, we examined the efficacy of rhTPO after allo-HSCT in children and adolescents.

Results: All of the children and adolescents underwent hematopoietic reconstruction. The median time to PLT engraftment was 16 days for all patients, with 14 (range, 11-24) days in the 0- to 9-year-old group and 16 (range, 11-41) days in the 10- to 17-year-old group; the difference was statistically significant (P < 0.05). The median time to neutrophil engraftment was 12 days in both groups. The median recovery times for PLT counts of ≥ 20 × 10⁹/L and ≥ 50 × 10⁹/L in the 0- to 9-year-old group were 10 (range, 2-20) and 11 (range, 2-20) days, respectively, and those for the 10- to 17-year-old group were 9 (range, 4-23) and 12 (range, 5-34) days, respectively. Children exhibited significantly shorter time to PLT engraftment (14 days vs 16 days) and shorter recovery time to PLT count ≥ 100 × 10⁹/L (16 days vs 18 days) (P < 0.05) than adolescents. The incidence of acute GVHD in all patients was 53.2%, with a higher incidence in children (61.1%) than in adolescents (46.5%). The incidence of chronic GVHD showed little difference between the two age groups, with an overall incidence of 10.1%. No adverse events, other than bleeding, were observed in either age group. The incidence of bleeding was 20.3%. The median follow-up time for all survivors was 573 days (range: 42-1803 days) after transplantation. At the final follow-up, 3 patients in the 0- to 9-year-old group died; however, none of these deaths were attributed to allo-HSCT or the use of rhTPO. All patients survived in the 10- to 17-year-old group.

Conclusion: rhTPO was not associated with any significant safety issues and was well tolerated by pediatric and adolescent patients with hematologic diseases who underwent allo-HSCT. Our results suggested that rhTPO may benefit allo-HSCT in children and adolescents by improving PLT recovery.

Keywords: Allogeneic hematopoietic stem cell transplantation; Graft-vs-host disease; Pediatric hematologic disorders; Platelet engraftment; Recombinant human thrombopoietin.

Figure 1

Median and median change of platelet after recombinant human thrombopoietin treatment from baseline in patients with hematological diseases in different age groups. A: Median platelet (PLT) over time; B: Median change of PLT from baseline. Data shown are median (Q1, Q3). Numbers under abscissa indicate time (day) after treatment with recombinant human thrombopoietin (rhTPO).