阿伐曲泊帕联合rhTPO在恶性血液病自体造血干细胞移植中的临床疗效分析*

doi:10.3969/j.issn.1671-2587.2024.06.017

临床输血与检验 ›› 2024, Vol. 26 ›› Issue (6): 812-817.DOI: 10.3969/j.issn.1671-2587.2024.06.017

阿伐曲泊帕联合rhTPO在恶性血液病自体造血干细胞移植中的临床疗效分析^*

明静, 丁凯阳, 胡茂贵, 王馨辰

中国科学技术大学附属第一医院西区血液科,安徽合肥 230031

收稿日期:2024-06-26 出版日期:2024-12-20 发布日期:2024-12-20
通讯作者: 丁凯阳,主要从事血液系统恶性肿瘤方面研究,（E-mail）dingkaiy@126.com。
作者简介:明静,主要从事血液系统恶性肿瘤方面研究,（E-mail）793007858@qq.com。
基金资助:
*本课题受安徽省卫生健康委员会重点项目（No.AHWJ2023A10056）资助

Efficacy of Avatrombopag Combined with rhTPO for Thrombocytopenia Treatment in Patients with Hematologic Malignancies after Autologous Hematopoietic Stem Cell Transplantation

MING Jing, DING Kaiyang, HU Maogui, WANG Xinchen

Department of Hematology, the First Affiliated Hospital of USTC,Anhui Provincial Cancer Hospital, Division of Life Sciences And Medicine, University of Science and Technology of China, Hefei, 230031

Received:2024-06-26 Online:2024-12-20 Published:2024-12-20

摘要/Abstract

摘要： 目的观察阿伐曲泊帕联合重组人血小板生成素（rhTPO）对恶性血液病自体造血干细胞移植（ASCT）后血小板（PLT）植入的临床疗效。方法回顾性分析76例ASCT患者的临床资料,其中40例阿伐曲泊帕（avatrombopag, AVA）联合rhTPO升血小板治疗为观察组,36例rhTPO单药治疗为对照组。比较两组患者PLT水平、PLT植入时间、PLT输注数量、PLT谷值及Ⅳ级血小板减少持续时间,记录不良反应。结果观察组PLT植入时间短于对照组[（11.15±1.08）d vs.（12.61±2.65）d,（P<0.05）],且PLT输注单位数少于对照组[2（1.00,2.75）U vs. 3（2.00,4.00）U,（P<0.001）];阿伐曲泊帕联合rhTPO促血小板治疗的第5天、第10天、第15天,血小板计数均高于相应单药对照组,药物干预后的第5天及第10天血小板植入率有所提高（P<0.05）。多元线性回归分析显示,阿伐曲泊帕是影响PLT植入时间的独立因素（P<0.001）,其使用可将植入时间缩短1.598天。两组患者均观察到出血事件,以皮肤黏膜出血点、瘀斑、牙龈出血为主,出血发生率无差异。两组均无血栓形成及凝血障碍发生。结论阿伐曲泊帕联合rhTPO能有效升高ASCT患者PLT计数,促进PLT植入,二者联用有协同作用,且耐受良好。

关键词: 自体造血干细胞移植, 阿伐曲泊帕, 化疗所致血小板减少症, 血小板植入, 重组人血小板生成素

Abstract: Objective To observe efficacy of avatrombopag (AVA) combined with recombinant human thrombopoietin (rhTPO) on platelet (PLT) engraftment in patients with hematological malignancies after autologous hematopoietic stem cell transplantation (ASCT/auto-HSCT). Methods Seventy-six ASCT patients were retrospectively collected, including 40 patients treated with AVA with rhTPO as observation group, and 36 patients treated with rhTPO alone as control group. PLT count, engraftment time, number of PLT transfused, platelet nadir and duration at grade IV thrombocytopenia were compared, and adverse reactions were recorded. Results The PLT engraftment time in observation group was shorter than that in control group (11.15±1.08 vs.12.61±2.65 days, P<0.05), and the number of PLT transfused units was less [2 (1.00,2.75) units vs. 3 (2.00, 4.00) units], (P<0.001). PLT counts on day 5, day 10 and day 15 in observation group were higher than that in control group, and the rates of platelet engraftment on days 5 and 10 were significantly higher (P<0.05). Multiple linear regression analysis showed that AVA was an independent factor (P<0.001), and its use shortened the engraftment time by 1.598 days. Bleeding events were observed in both groups, mainly in petechiae、ecchymosis or gingival bleeding, and no difference in bleeding rate. No thrombosis and coagulation disorders occurred in both groups. Conclusion AVA combined with rhTPO effectively increased PLT count and promoted PLT engraftment. The combination of the two has a synergistic effect and is well tolerated.

Key words: Autologous hematopoietic stem cell transplantation, Avatrombopag, Chemotherapy-induced thrombocytopenia, Platelet engraftment, Recombinant human thrombopoietin

中图分类号:

R457
R55

明静, 丁凯阳, 胡茂贵, 王馨辰. 阿伐曲泊帕联合rhTPO在恶性血液病自体造血干细胞移植中的临床疗效分析^*[J]. 临床输血与检验, 2024, 26(6): 812-817.

MING Jing, DING Kaiyang, HU Maogui, WANG Xinchen. Efficacy of Avatrombopag Combined with rhTPO for Thrombocytopenia Treatment in Patients with Hematologic Malignancies after Autologous Hematopoietic Stem Cell Transplantation[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(6): 812-817.

参考文献

[1] DHAKAL B,SZABO A,CHHABRA S,et al.Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction:a systematic review and meta-analysis[J]. JAMA Oncol,2018,4(3):343-350.
[2] ZAHID U,AKBAR F,AMARANENI A,et al.A review of autologous stem cell transplantation in lymphoma[J]. Curr Hematol Malig Rep,2017,12(3):217-226.
[3] CHELOFF A Z,AL-SAMKARI H.Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease[J]. J Blood Med,2019,10:313-321.
[4] AL-SAMKARI H.Avatrombopag maleate for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease[J]. Drugs Today, 2018,54(11):647-655.
[5] 徐慧,赵洋,马雅婷,等. 阿伐曲泊帕与重组人血小板生成素治疗肿瘤化疗所致血小板减少症的疗效及安全性[J]. 中华实用诊断与治疗杂志,2022,36(10):1073-1076.
[6] 王玲燕,金剑英,谢静静,等. 阿伐曲泊帕治疗肿瘤治疗相关血小板减少症的疗效及耐受性研究[J]. 浙江医学, 2023,45(14):1528-1531.
[7] Common Terminology Criteria for Adverse Events (CTCAE) Version5.0. [EB/OL].(2017-11-27).https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.
[8] PARRONDO R D,AILAWADHI S,SHER T,et al.Autologous stem-cell transplantation for multiple myeloma in the era of novel therapies[J]. JCO Oncol Pract,2020,16(2):56-66.
[9] TRICOT G,JAGANNATH S,VESOLE D,et al.Peripheral blood stem cell transplants for multiple myeloma:identification of favorable variables for rapid engraftment in 225 patients[J]. Blood,1995,85(2):588-596.
[10] KARLSTRÖM C,GRYFELT G,SCHMIED L,et al. Platelet transfusion improves clot formation and platelet function in severely thrombocytopenic haematology patients[J]. Br J Haematol,2022,196(1):224-233.
[11] ZHU Q H,YANG S M,ZENG W B,et al.A real-world observation of eltrombopag and recombinant human thrombopoietin (rhTPO) in lymphoma patients with chemotherapy induced thrombocytopenia[J]. Front Oncol,2021,11:701539.
[12] LI Q W,YE M,XIAO W H,et al.Prophylactic recombinant human thrombopoietin treatment alleviates chemotherapy- induced thrombocytopenia in tumor patients[J]. J South Med Univ,2012,32(7):1064-1066.
[13] ZHANG J J,ZHAO R,XIA F,et al.Cost-effectiveness analysis of rhTPO and rhIL-11 in the treatment of chemotherapy-induced thrombocytopenia in hematological tumors based on real-world data[J]. Ann Palliat Med,2022,11(8):2709-2719.
[14] YANG J L,SHI Y K,HE X H,et al.Evaluation of the role of rhIL-11 on hematological recovery in lymphoma patients after autologous hematopoietic stem cell transplantation[J]. Chin J Oncol,2012,34(6):469-472.
[15] GU J L,LIU J R,LI X Z,et al.Recombinant human thrombopoietin improved platelet engraftment after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma[J]. Cancer Med,2021,10(21):7641-7649.
[16] SCORDO M,GILBERT L J,HANLEY D M,et al.Open-label pilot study of romiplostim for thrombocytopenia after autologous hematopoietic cell transplantation[J].Blood Adv,2023,7(8):1536-1544.
[17] ZHU L D,LIU J,KONG P Y,et al.Analysis of the efficacy and safety of avatrombopag combined with MSCs for the treatment of thrombocytopenia after allogeneic hematopoietic stem cell transplantation[J]. Front Immunol,2022,13:910893.
[18] ZHOU M,QI J Q,GU C Y,et al.Avatrombopag for the treatment of thrombocytopenia post hematopoietic stem-cell transplantation[J]. Ther Adv Hematol,2022, 13:20406207221127532.
[19] RUAN Y S,CAO W,LUO T T,et al.Avatrombopag for the treatment of thrombocytopenia in children's patients following allogeneic hematopoietic stem-cell transplantation:a pilot study[J]. Front Pediatr,2023, 11:1099372.
[20] FUKUSHIMA-SHINTANI M,SUZUKI K,IWATSUKI Y,et al.AKR-501 (YM477) in combination with thrombopoietin enhances human megakaryocytopoiesis[J]. Exp Hematol,2008, 36(10): 1337-1342.
[21] SONG A B,AL-SAMKARI H.Emerging data on thrombopoietin receptor agonists for management of chemotherapy-induced thrombocytopenia[J]. Expert Rev Hematol,2023,16(5):365-375.
[22] LOZANO M L,RODEGHIERO F.Thrombopoietin receptor agonist in chemotherapy-induced thrombocytopenia[J]. Lancet Haematol,2022,9(3): e168-e169.
[23] AL-SAMKARI H,KOLB-SIELECKI J,SAFINA S Z,et al.Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies:an international,randomised,double-blind,placebo-controlled,phase 3 trial[J]. Lancet Haematol,2022,9(3):e179-e189.
[24] GILREATH J,LO M,BUBALO J.Thrombopoietin receptor agonists (TPO-RAs):drug class considerations for pharmacists[J]. Drugs,2021,81(11):1285-1305.
[25] CUI Y Y,HE Y F,HU C L,et al.Avatrombopag for the treatment of thrombocytopenia induced by chemotherapy in patients with solid tumors:a multicenter,open-label,single-arm trial[J]. Front Pharmacol,2022,13:970978.
[26] KUTER D J.Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies[J]. Haematologica,2022, 107(6):1243-1263.
[27] GAO Y T,LIU Q,SHEN Y Y,et al.Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors[J]. Platelets,2022, 33(7):1024-1030.
[28] TSYKUNOVA G,GHANIMA W.Avatrombopag for the treatment of adult patients with chronic immune thrombocytopenia (cITP):focus on patient selection and perspectives[J]. Ther Clin Risk Manag,2022,18:273-286.
[29] DŁUGOSZ-DANECKA M,ZDZIARSKA J,JURCZAK W. Avatrombopag for the treatment of immune thrombocytopenia[J]. Expert Rev Clin Immunol,2019, 15(4):327-339.
[30] XU H M,CAI R.Avatrombopag for the treatment of thrombocytopenia in patients with chronic liver disease[J]. Expert Rev Clin Pharmacol,2019,12(9): 859-865.

阿伐曲泊帕联合rhTPO在恶性血液病自体造血干细胞移植中的临床疗效分析^*

Efficacy of Avatrombopag Combined with rhTPO for Thrombocytopenia Treatment in Patients with Hematologic Malignancies after Autologous Hematopoietic Stem Cell Transplantation

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