Thrombopoietin Level Predicts the Response to Avatrombopag Treatment for Persistent Thrombocytopenia After Haploidentical Haematopoietic Stem Cell Transplantation

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2023 Sep 7

PMID 37679646

Authors

Haixia Fu

Meng Lv

Huixin Liu

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

Affiliations

Soon will be listed here.

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 × 10/L or 50 × 10/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.

References

Zhao X, Zhao X, Huo M, Fan Q, Pei X, Wang Y . Donor-Specific Anti-Human Leukocyte Antigen Antibodies Predict Prolonged Isolated Thrombocytopenia and Inferior Outcomes of Haploidentical Hematopoietic Stem Cell Transplantation. J Immunol Res. 2017; 2017:1043836. PMC: 5412255. DOI: 10.1155/2017/1043836. View

Akahoshi Y, Kimura S, Gomyo A, Hayakawa J, Tamaki M, Harada N . Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft-versus-host disease and survival outcome. Hematol Oncol. 2017; 36(1):276-284. DOI: 10.1002/hon.2427. View

Sun Y, Wang Y, Wang F, Yan C, Cheng Y, Chen Y . Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor. Front Med (Lausanne). 2021; 8:604085. PMC: 8212968. DOI: 10.3389/fmed.2021.604085. View

de Sauvage F, Villeval J, Shivdasani R . Regulation of megakaryocytopoiesis and platelet production: lessons from animal models. J Lab Clin Med. 1998; 131(6):496-501. DOI: 10.1016/s0022-2143(98)90057-9. View

Kaushansky K, Lok S, Holly R, Broudy V, Lin N, BAILEY M . Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature. 1994; 369(6481):568-71. DOI: 10.1038/369568a0. View

Gurney A, de Sauvage F, Moore M . Thrombocytopenia in c-mpl-deficient mice. Science. 1994; 265(5177):1445-7. DOI: 10.1126/science.8073287. View

Fu H, Zhang X, Xu L, Liu K, Huang X . Characterization of thrombopoietin kinetics within 60 days after allogeneic hematopoietic stem cell transplantation and its correlation with megakaryocyte ploidy distribution. Clin Transplant. 2015; 30(2):170-8. DOI: 10.1111/ctr.12673. View

Zhang X, Fu H, Xu L, Liu D, Wang J, Liu K . Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes. Biol Blood Marrow Transplant. 2010; 17(2):274-80. DOI: 10.1016/j.bbmt.2010.09.007. View

Erickson-Miller C, Delorme E, Tian S, Hopson C, Landis A, Valoret E . Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2008; 27(2):424-30. PMC: 2729672. DOI: 10.1634/stemcells.2008-0366. View

10.

Bento L, Bastida J, Garcia-Cadenas I, Garcia-Torres E, Rivera D, Bosch-Vilaseca A . Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2019; 25(9):1825-1831. DOI: 10.1016/j.bbmt.2019.05.023. View

11.

Sun Y, Kong Y, Zhang X, Wang Y, Shi M, Song Y . A novel recombinant human thrombopoietin for treating prolonged isolated thrombocytopenia after allogeneic stem cell transplantation. Platelets. 2018; 30(8):994-1000. DOI: 10.1080/09537104.2018.1557613. View

12.

Wang Y, Liu Q, Xu L, Liu K, Zhang X, Ma X . Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood. 2015; 125(25):3956-62. DOI: 10.1182/blood-2015-02-627786. View

13.

Xiao-Jun H, Lan-Ping X, Kai-Yan L, Dai-Hong L, Yu W, Huan C . Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res. 2009; 15(14):4777-83. DOI: 10.1158/1078-0432.CCR-09-0691. View

14.

Bashey A, Zhang X, Sizemore C, Manion K, Brown S, Holland H . T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor.... J Clin Oncol. 2013; 31(10):1310-6. DOI: 10.1200/JCO.2012.44.3523. View

15.

Sun Y, He G, Chang Y, Xu L, Zhang X, Han W . The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation. Ann Hematol. 2015; 94(10):1699-705. DOI: 10.1007/s00277-015-2440-x. View

16.

Xu L, Chen H, Chen J, Han M, Huang H, Lai Y . The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China-recommendations from the Chinese Society of Hematology. J Hematol Oncol. 2018; 11(1):33. PMC: 5833104. DOI: 10.1186/s13045-018-0564-x. View

17.

Zhang X, Chen J, Han M, Huang H, Jiang E, Jiang M . The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update. J Hematol Oncol. 2021; 14(1):145. PMC: 8441240. DOI: 10.1186/s13045-021-01159-2. View

18.

Chang Y, Luznik L, Fuchs E, Huang X . How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation?. J Hematol Oncol. 2016; 9:35. PMC: 4830035. DOI: 10.1186/s13045-016-0265-2. View

19.

Shi M, Kong Y, Song Y, Sun Y, Wang Y, Zhang X . Atorvastatin enhances endothelial cell function in posttransplant poor graft function. Blood. 2016; 128(25):2988-2999. DOI: 10.1182/blood-2016-03-702803. View

20.

Markham A . Avatrombopag: A Review in Thrombocytopenia. Drugs. 2021; 81(16):1905-1913. PMC: 8610948. DOI: 10.1007/s40265-021-01613-y. View