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Eltrombopag in Immune Thrombocytopenia, Aplastic Anemia, and Myelodysplastic Syndrome: From Megakaryopoiesis to Immunomodulation.依鲁替尼在免疫性血小板减少症、再生障碍性贫血和骨髓增生异常综合征中的作用:从巨核细胞生成到免疫调节。
Drugs. 2019 Aug;79(12):1305-1319. doi: 10.1007/s40265-019-01159-0.
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Ann Hematol. 2019 Jun;98(6):1341-1350. doi: 10.1007/s00277-019-03652-8. Epub 2019 Mar 26.
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环孢素A联合重组人血小板生成素治疗非重型再生障碍性贫血的疗效评估

[Evaluation of the efficacy of cyclosporin A combined with recombined human thrombopoietin for treating patients with non-severe aplastic anemia].

作者信息

Zhang M L, Chen W S, Han B

机构信息

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences, Beijing 100730, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2020 Aug 14;41(8):637-642. doi: 10.3760/cma.j.issn.0253-2727.2020.08.004.

DOI:10.3760/cma.j.issn.0253-2727.2020.08.004
PMID:32942816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7525171/
Abstract

To compare the efficacy of cyclosporin A (CsA) alone and CsA combined with recombined human thrombopoietin (rhTPO) in patients with non-severe aplastic anemia (NSAA) . Data from 83 patients with NSAA between August 2014 and February 2019 were collected retrospectively. The study population included 35 men and 48 women, with a median age of 45 years (14-85 years) . Among them, 57 had been treated with CsA + rhTPO, TPO was administered at 15 000 U QD for 7 days, once a month for 3 months, and the other 26 patients with compatible baseline characters were treated with CsA alone. All the enrolled patients had been treated with CsA for at least 6 months and were followed up for at least 1 year. The efficacy and outcome were compared between the two groups. Total 23 men and 34 women, with a median age of 46 years (14-85 years) were treated with CsA + rhTPO. The median duration of CsA treatment was 17 (8-28) months, and the patients were followed up for a median of 27 (12-45) months. Total 12 men and 14 women, with a median age of 40 years (20-64) were treated with CsA alone. The median duration of CsA treatment was 19 months (9-30 months) , and the median follow-up duration was 29 months (16-66 months) . There was no significant difference in the baseline characteristics of the two groups (>0.05) . There was no significant difference in the CR and OR rates of the two groups at 1, 3, 6, 12, and 24 months of treatment (>0.05) . The change in the platelet level for the CsA + rhTPO treated group after 1 month[8 (-12-86) ×10(9)/L 3 (16-57) ×10(9)/L, =0.029) , 3 months[24 (-6-102) ×10(9)/L 7 (-9-76) ×10(9)/L, =0.006], and 6 months[33.5 (-4-123) ×10(9)/L 12.5 (-14-109) ×10(9)/L, =0.048] of treatment was higher than that in the CsA alone group, while no significant difference was found between the two groups at other time points. There was no significant difference in the change in the megakaryocyte level between the two groups[3 (0-4) 2 (0-5) , =-0.868, =0.385] after 6 months of treatment. Apart from 10.5% (6/57) of the patients in the CsA + rhTPO treated group who reported soreness at the injection site, there was no other significant difference between the two groups in terms of adverse effects. During the follow-up period, there were two cases of increasing paroxysmal nocturnal hemoglobinuria clone to over 10%, one in the CsA + rhTPO treated group, the other in the CsA alone group; and there was one case of progression to SAA in the CsA + rhTPO treated group; while no case of death or thromboembolic event (TEE) , fibrosis or reticulin proliferation, progression to myelodysplastic syndrome (MDS) , or acute myeloid leukemia was observed in either group. There was one case of progression to SAA in the CsA + rhTPO treated group but none in the CsA alone group. Compared to CsA alone, CsA + rhTPO treatment can accelerate the recovery of the platelet level with acceptable adverse effects.

摘要

比较环孢素A(CsA)单药与CsA联合重组人血小板生成素(rhTPO)治疗非重型再生障碍性贫血(NSAA)患者的疗效。回顾性收集2014年8月至2019年2月期间83例NSAA患者的数据。研究人群包括35例男性和48例女性,中位年龄45岁(14 - 85岁)。其中,57例接受CsA + rhTPO治疗,TPO按15000 U每日1次给药,共7天,每月1次,共3个月,另外26例具有匹配基线特征的患者仅接受CsA治疗。所有入组患者均接受CsA治疗至少6个月,并随访至少1年。比较两组的疗效和结局。共有23例男性和34例女性,中位年龄46岁(14 - 85岁)接受CsA + rhTPO治疗。CsA治疗的中位持续时间为17(8 - 28)个月,患者中位随访27(12 - 45)个月。共有12例男性和14例女性,中位年龄40岁(20 - 64岁)仅接受CsA治疗。CsA治疗的中位持续时间为19个月(9 - 30个月),中位随访时间为29个月(16 - 66个月)。两组的基线特征无显著差异(>0.05)。治疗1、3、6、12和24个月时,两组的完全缓解(CR)率和部分缓解(OR)率无显著差异(>0.05)。CsA + rhTPO治疗组治疗1个月后血小板水平变化[8(-12 - 86)×10⁹/L对3(16 - 57)×10⁹/L,P = 0.029]、3个月后[24(-6 - 102)×10⁹/L对7(-9 - 76)×10⁹/L,P = 0.006]和6个月后[33.5(-4 - 123)×10⁹/L对12.5(-14 - 109)×10⁹/L,P = 0.048]高于CsA单药组,而其他时间点两组间无显著差异。治疗6个月后两组巨核细胞水平变化无显著差异[3(0 - 4)对2(0 - 5),P = -0.868,P = 0.385]。除CsA + rhTPO治疗组10.5%(6/57)的患者报告注射部位疼痛外,两组在不良反应方面无其他显著差异。随访期间,有2例阵发性夜间血红蛋白尿克隆增加至超过10%,1例在CsA + rhTPO治疗组,另1例在CsA单药组;CsA + rhTPO治疗组有1例进展为重型再生障碍性贫血(SAA);而两组均未观察到死亡或血栓栓塞事件(TEE)、纤维化或网状纤维增生、进展为骨髓增生异常综合征(MDS)或急性髓系白血病的病例。CsA + rhTPO治疗组有1例进展为SAA,而CsA单药组无。与CsA单药相比,CsA + rhTPO治疗可加速血小板水平恢复,且不良反应可接受。