Recombinant human thrombopoietin promotes platelet engraftment after haploidentical hematopoietic stem cell transplantation: a prospective randomized controlled trial

Abstract

Delayed platelet engraftment (DPE) is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This phenomenon is also a predictor of increased treatment-related mortality and poor survival. Therefore, therapies that promote platelet engraftment to prevent DPE are needed. This prospective randomized controlled trial was designed to investigate whether recombinant human thrombopoietin (rhTPO), administered subcutaneously at a daily dose of 15,000 U from the first day after transplantation, promotes platelet engraftment after haploidentical HSCT. The cumulative incidence of platelet engraftment (platelet recovery to ≥20×10 9 /L without transfusion support for seven consecutive days) on day 60 posttransplantation was significantly higher in the rhTPO group (n=60) than in the control group (n=60) (91.7±3.8 % vs. 74.5 ±5.8 %, P=0.041). Additionally, the number of platelet transfusions from day 14 to day 60 was significantly lower in the rhTPO group than in the control group (4±5 vs. 7±9 Units, P=0.018). No severe adverse effects were observed, with a median follow-up duration of 256 days (range, 48-586 days). The incidences of acute graft-versus-host disease (GVHD), chronic GVHD, and cytomegalovirus viremia and the probabilities of overall survival and disease-free survival did not differ between the two groups. A multivariate analysis of all patients revealed that regardless of assignment to the rhTPO group or the control group (hazard ratio (HR)=1.514; 95 % CI (1.024-2.238); P=0.038), the number of total infused CD34 + cells (HR=1.304; 95 % CI (1.148-1.482); P<0.001) and slower neutrophil engraftment (HR=2.777; 95 % CI (1.841-4.189); P<0.001) were associated with platelet engraftment. In conclusion, rhTPO promotes platelet engraftment and safely reduces the requirement for platelet transfusion in patients after unmanipulated haploidentical HSCT. This trial was registered with the Chinese Clinical Trial Registry (www.chictr. org) as ChiCTR-TRC-11001774. http://www.chictr.org/cn/ proj/show.aspx?proj=2132.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment and Improves Prognosis of Patients with Myelodysplastic Syndromes and Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation

“…However, when we stratified patients by disease type, we found that rhTPO significantly improved the OS of patients with MDS or AA. The results of our study are different from those reported by Han et al [24], in which rhTPO did not improve the prognosis of patients after allo-HSCT. The main reason for this difference may be that different patient populations were selected.…”

“…The initial survival analysis of the entire cohort indicated that the use of rhTPO held no prognostic significance, as the OS of patients who received rhTPO was similar to that of patients who did not. These data are consistent with a report from Han et al, in which probabilities of OS and disease-free survival in patients after haploidentical HSCT did not differ between the rhTPO and non-rhTPO groups [24]. However, when we stratified patients by disease type, we found that rhTPO significantly improved the OS of patients with MDS or AA.…”

“…However, few studies have reported the clinical effect of rhTPO on platelet engraftment in patients after allo-HSCT. One prospective randomized controlled study from Han et al [24] indicated that rhTPO promotes platelet engraftment in patients after haploidentical HSCT. This view was supported by our current study, which included more patients, more disease types, and different types of allo-HSCT (matched sibling donors, unrelated donors, and haploidentical donors).…”

“…The main reason for this difference may be that different patient populations were selected. In the study from Han et al [24], no patients with MDS or AA were included. Furthermore, only patients who received haploidentical HSCT were analyzed in that study, unlike our study, which included haploidentical HSCT and non-haploidentical HSCT.…”

“…The safety of recombinant human TPO (rhTPO) has been demonstrated in many previous trials [21][22][23]. A recent prospective randomized controlled trial from Peking University reported that rhTPO after haploidentical HSCT promoted platelet engraftment and reduced the requirement for platelet transfusion [24]. Subsequently, the same group reported a correlation between endogenous TPO levels and platelet recovery after allo-HSCT and the prognostic significance of TPO levels [25].…”