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

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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 × 109/L without transfusion support for seven consecutive days) on day 60 post-transplantation 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.

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Acknowledgments

The authors would like to thank the patients for their involvement in the trial and are grateful for grant support from the National Natural Science Foundation of China (Grant No. 30971292), the Natural Science Foundation of Beijing (Grant No. 7122193), the National High Technology Research and Development Program of China (Program 863) (Grant No. 2011AA020105), the Clinical Subject’s Key Project of the Ministry of Health, and the National Natural Science Foundation of China (Grant No. 30725038). The authors thank American Journal Experts (www.journalexperts.com) for their assistance in editing this manuscript.

Conflict of interest

All authors declare no competing financial interests.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China

    Ting-ting Han, Lan-ping Xu, Dai-hong Liu, Kai-yan Liu, Feng-rong Wang, Yu Wang, Chen-hua Yan, Yu-hong Chen, Yu-qian Sun, Yu Ji, Jing-zhi Wang, Xiao-hui Zhang & Xiao-jun Huang

  2. Peking-Tsinghua Center for Life Sciences, Beijing, China

    Xiao-jun Huang

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  1. Ting-ting Han
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  2. Lan-ping Xu
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Correspondence to Xiao-jun Huang.

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Ting-ting Han and Lan-ping Xu share the first authorship.

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Han, Tt., Xu, Lp., Liu, Dh. et al. Recombinant human thrombopoietin promotes platelet engraftment after haploidentical hematopoietic stem cell transplantation: a prospective randomized controlled trial. Ann Hematol 94, 117–128 (2015). https://doi.org/10.1007/s00277-014-2158-1

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  • DOI: https://doi.org/10.1007/s00277-014-2158-1

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