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Thrombopoietin level predicts the response to avatrombopag treatment for persistent thrombocytopenia after haploidentical haematopoietic stem cell transplantation

Bone Marrow Transplantation volume 58, pages 1368–1376 (2023)Cite this article

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Abstract

Persistent thrombocytopenia (PT) has an unsatisfactory response to therapy after haploidentical haematopoietic stem cell transplantation (haplo-HSCT). We retrospectively evaluated the safety and efficacy of avatrombopag treatment in 69 patients with PT following haplo-HSCT and assessed whether baseline thrombopoietin (TPO) levels could predict treatment response. Overall response (OR) and complete response (CR) were defined as increased platelet levels to over 20 × 109/L or 50 × 109/L independent of platelet transfusion during or within 7 days of the end of avatrombopag treatment, respectively. The incidences of OR and CR were 72.5% and 58.0%, with a median of 11 and 29 days to OR and CR, respectively. ROC analysis suggested that the optimally discriminant baseline TPO level threshold for both OR and CR to avatrombopag was ≤ 1714 pg/mL. In multivariate analysis, a lower baseline TPO level (P = 0.005) was a significant independent factor of response to avatrombopag. For patients resistant to other TPO receptor agonists (TPO-RAs), 9/16 (56.3%) exhibited a response after switching to avatrombopag. Avatrombopag was well tolerated, and responders achieved improved overall survival (79.0% vs. 91.1%, P = 0.001). In conclusion, avatrombopag is a potential safe and effective treatment for PT after haplo-HSCT, and lower baseline TPO levels predicted a better response.

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Fig. 1: Flow of patient enrollment.
Fig. 2: The baseline endogenous TPO levels and the cumulative incidence of response of avatrombopag.
Fig. 3: The predicted value of endogenous TPO levels.
Fig. 4: The cumulative incidence of OR.
Fig. 5: OS after avatrombopag treatment.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

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Acknowledgements

We appreciate the participating investigators and patients.

Funding

This work was supported by National Key Research and Development Program of China (No. 2021YFC2500304), Key Program of National Natural Science Foundation of China (No. 82230004), National Natural Science Foundation of China (No. 81970113), Beijing Natural Science Foundation (No.7232188) and the Capital Health Research and Development of Special (No. 2022-1-4082) and MOE Engineering Center of Hematological Disease, Soochow University.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Haematology, Beijing, China

    Haixia Fu, Meng Lv, Yuqian Sun, Yuanyuan Zhang, Xiaodong Mo, Tingting Han, Fengrong Wang, Chenhua Yan, Yu Wang, Jun Kong, Wei Han, Huan Chen, Yao Chen, Yuhong Chen, Lanping Xu, Kaiyan Liu, Xiaojun Huang & Xiaohui Zhang

  2. Collaborative Innovation Center of Haematology, Peking University, Beijing, China

    Haixia Fu, Meng Lv, Yuqian Sun, Yuanyuan Zhang, Xiaodong Mo, Tingting Han, Fengrong Wang, Chenhua Yan, Yu Wang, Jun Kong, Wei Han, Huan Chen, Yao Chen, Yuhong Chen, Lanping Xu, Kaiyan Liu, Xiaojun Huang & Xiaohui Zhang

  3. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Haixia Fu, Meng Lv, Yuqian Sun, Yuanyuan Zhang, Xiaodong Mo, Tingting Han, Fengrong Wang, Chenhua Yan, Yu Wang, Jun Kong, Wei Han, Huan Chen, Yao Chen, Yuhong Chen, Lanping Xu, Kaiyan Liu, Xiaojun Huang & Xiaohui Zhang

  4. National Clinical Research Center for Haematologic Disease, Beijing, China

    Haixia Fu, Meng Lv, Yuqian Sun, Yuanyuan Zhang, Xiaodong Mo, Tingting Han, Fengrong Wang, Chenhua Yan, Yu Wang, Jun Kong, Wei Han, Huan Chen, Yao Chen, Yuhong Chen, Lanping Xu, Kaiyan Liu, Xiaojun Huang & Xiaohui Zhang

  5. Peking University People’s Hospital, Department of Clinical Epidemiology and Biostatistics, Beijing, China

    Huixin Liu

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  1. Haixia Fu
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Contributions

XHZ contributed to the study design. HXF contributed to the data analysis and manuscript writing. HXL contributed to data analysis. All authors contributed to the study execution and data collection. All authors provided a full review of the article and are fully responsible for all content and editorial decisions, were involved in all stages of manuscript development, and have approved the final version.

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Correspondence to Xiaohui Zhang.

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Fu, H., Lv, M., Liu, H. et al. Thrombopoietin level predicts the response to avatrombopag treatment for persistent thrombocytopenia after haploidentical haematopoietic stem cell transplantation. Bone Marrow Transplant 58, 1368–1376 (2023). https://doi.org/10.1038/s41409-023-02100-6

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