Dong-Mei Han, Li Ding, Xiao-Li Zheng, Hong-Min Yan, Mei Xue, Jing Liu, Ling Zhu, Sheng Li, Heng-Xiang Wang
{"title":"单倍体造血干细胞移植联合间充质基质细胞治疗获得性重度再生障碍性贫血127例报告","authors":"Dong-Mei Han, Li Ding, Xiao-Li Zheng, Hong-Min Yan, Mei Xue, Jing Liu, Ling Zhu, Sheng Li, Heng-Xiang Wang","doi":"10.19746/j.cnki.issn.1009-2137.2022.04.041","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To analyze the prognostic factors of haplo-HSCT combined with MSC in the treatment of SAA.</p><p><strong>Methods: </strong>127 SAA patients who had undergone haplo-HSCT with co-infusion of MSC in our center from January 2014 to August 2019 were analyzed retrospectively. Median age was 11 (1-37) years, and median follow-up time was 39.8 (1-74) months.</p><p><strong>Results: </strong>The median time for neutrophil and platelet engraftment was 14 d and 18 d respectively. The cumulative incidences of grade III-IV aGVHD was 4.4%±1.9% at day +100. The 2-year cumulative incidence of extensive cGVHD was 8.3%± 2.7%. The estimated 3-year OS was 86.1%±3.1%. Univariate analysis showed that high-dose CD34<sup>+</sup> cells (>6.69×106/kg) could promote the engraftment of neutrophil (97.9%±0.05% vs 88.6%±0.13% at day +21, P=0.0006) and platelet (81.2%±0.33% vs 70.8%±0.26% at day +28, P=0.002) and did not increase the incidence of aGVHD (10.4%±0.1% vs 18.9%±0.1% at day +100, P=0.18). More nucleated cells (>12.78×10<sup>8</sup>/kg) caused a lower incidence of grade II-IV aGVHD (8.6%±0.13% vs 21.7%±0.25% at day+100, P=0.04) and a higher incidence of 3-year OS (91.3%±3.2% vs 78.1%±6.5%, P=0.03) than less nucleated cells (≤12.78×10<sup>8</sup>/kg). Younger patients (age≤12 y) had faster neutrophil engraftment (94.9%±0.06% vs 87.5%±0.24% at day+21, P=0.02), higher 3-year OS (93.6%±2.8% vs 75.9%±6.4%, P=0.006) and higher 3-year FFS (93.6%±2.8% vs 68.3%±7.1%, P=0.000) than older patients (age>12 y). The shorter the time from diagnosis to HSCT (≤29.5 months), the higher the 3-year FFS of patients (88.8%±3.5% vs 74.2%±7.2%, P=0.028). Male patients with female donors had higher cumulative incidence of extensive cGVHD than others (20.0%±0.8% vs 4.6%±0.1%, P=0.01).</p><p><strong>Conclusion: </strong>In the haplo-HSCT of SAA, the prognosis of children patients is better than that of adults patients. More CD34<sup>+</sup> cells and nucleated cells can promote engraftment, reduce the incidence of aGVHD and improve OS. HSCT should be performed as early as possible, and the occurrence of cGVHD should be reduced in male patients by avoiding female donors.</p>","PeriodicalId":519535,"journal":{"name":"Zhongguo shi yan xue ye xue za zhi","volume":" ","pages":"1230-1237"},"PeriodicalIF":0.0000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Haploidentical Hematopoietic Stem Cell Transplantation with Co-Infusion of Mesenchymal Stromal Cells for Acquired Severe Aplastic Anemia: A Report of 127 Cases].\",\"authors\":\"Dong-Mei Han, Li Ding, Xiao-Li Zheng, Hong-Min Yan, Mei Xue, Jing Liu, Ling Zhu, Sheng Li, Heng-Xiang Wang\",\"doi\":\"10.19746/j.cnki.issn.1009-2137.2022.04.041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To analyze the prognostic factors of haplo-HSCT combined with MSC in the treatment of SAA.</p><p><strong>Methods: </strong>127 SAA patients who had undergone haplo-HSCT with co-infusion of MSC in our center from January 2014 to August 2019 were analyzed retrospectively. Median age was 11 (1-37) years, and median follow-up time was 39.8 (1-74) months.</p><p><strong>Results: </strong>The median time for neutrophil and platelet engraftment was 14 d and 18 d respectively. The cumulative incidences of grade III-IV aGVHD was 4.4%±1.9% at day +100. The 2-year cumulative incidence of extensive cGVHD was 8.3%± 2.7%. The estimated 3-year OS was 86.1%±3.1%. Univariate analysis showed that high-dose CD34<sup>+</sup> cells (>6.69×106/kg) could promote the engraftment of neutrophil (97.9%±0.05% vs 88.6%±0.13% at day +21, P=0.0006) and platelet (81.2%±0.33% vs 70.8%±0.26% at day +28, P=0.002) and did not increase the incidence of aGVHD (10.4%±0.1% vs 18.9%±0.1% at day +100, P=0.18). More nucleated cells (>12.78×10<sup>8</sup>/kg) caused a lower incidence of grade II-IV aGVHD (8.6%±0.13% vs 21.7%±0.25% at day+100, P=0.04) and a higher incidence of 3-year OS (91.3%±3.2% vs 78.1%±6.5%, P=0.03) than less nucleated cells (≤12.78×10<sup>8</sup>/kg). Younger patients (age≤12 y) had faster neutrophil engraftment (94.9%±0.06% vs 87.5%±0.24% at day+21, P=0.02), higher 3-year OS (93.6%±2.8% vs 75.9%±6.4%, P=0.006) and higher 3-year FFS (93.6%±2.8% vs 68.3%±7.1%, P=0.000) than older patients (age>12 y). The shorter the time from diagnosis to HSCT (≤29.5 months), the higher the 3-year FFS of patients (88.8%±3.5% vs 74.2%±7.2%, P=0.028). Male patients with female donors had higher cumulative incidence of extensive cGVHD than others (20.0%±0.8% vs 4.6%±0.1%, P=0.01).</p><p><strong>Conclusion: </strong>In the haplo-HSCT of SAA, the prognosis of children patients is better than that of adults patients. More CD34<sup>+</sup> cells and nucleated cells can promote engraftment, reduce the incidence of aGVHD and improve OS. HSCT should be performed as early as possible, and the occurrence of cGVHD should be reduced in male patients by avoiding female donors.</p>\",\"PeriodicalId\":519535,\"journal\":{\"name\":\"Zhongguo shi yan xue ye xue za zhi\",\"volume\":\" \",\"pages\":\"1230-1237\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Zhongguo shi yan xue ye xue za zhi\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.19746/j.cnki.issn.1009-2137.2022.04.041\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zhongguo shi yan xue ye xue za zhi","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.19746/j.cnki.issn.1009-2137.2022.04.041","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
目的:分析单倍造血干细胞联合骨髓间充质干细胞治疗SAA的预后因素。方法:回顾性分析2014年1月至2019年8月在我中心行单倍造血干细胞移植联合输注MSC的127例SAA患者。中位年龄11(1-37)岁，中位随访时间39.8(1-74)个月。结果:中性粒细胞和血小板植入的中位时间分别为14 d和18 d。在第100天，III-IV级aGVHD的累积发病率为4.4%±1.9%。2年累积广泛性cGVHD发生率为8.3%±2.7%。估计3年OS为86.1%±3.1%。单因素分析显示，高剂量CD34+细胞(>6.69×106/kg)可促进中性粒细胞(97.9%±0.05% vs 88.6%±0.13%，+21天，P=0.0006)和血小板(81.2%±0.33% vs 70.8%±0.26%，+28天，P=0.002)的植入，而不增加aGVHD的发生率(10.4%±0.1% vs 18.9%±0.1%，+100天，P=0.18)。有核细胞较多(>12.78×108/kg)导致II-IV级aGVHD发生率较低(第100天8.6%±0.13% vs 21.7%±0.25%，P=0.04)， 3年OS发生率高于有核细胞较少(≤12.78×108/kg)(91.3%±3.2% vs 78.1%±6.5%，P=0.03)。年轻患者(年龄≤12岁)中性粒细胞移植速度更快(94.9%±0.06% vs 87.5%±0.24% +21天，P=0.02)， 3年OS(93.6%±2.8% vs 75.9%±6.4%，P=0.006)和3年FFS(93.6%±2.8% vs 68.3%±7.1%，P=0.000)高于年龄>12岁的老年患者(诊断至HSCT时间≤29.5个月)，患者3年FFS越短(88.8%±3.5% vs 74.2%±7.2%，P=0.028)。男性女性供体患者广泛cGVHD累积发生率高于其他患者(20.0%±0.8% vs 4.6%±0.1%，P=0.01)。结论:在SAA的单倍hsct中，儿童患者的预后优于成人患者。更多的CD34+细胞和有核细胞可以促进移植，降低aGVHD的发生率，改善OS。应尽早进行HSCT，避免女性供体，减少男性患者cGVHD的发生。
[Haploidentical Hematopoietic Stem Cell Transplantation with Co-Infusion of Mesenchymal Stromal Cells for Acquired Severe Aplastic Anemia: A Report of 127 Cases].
Objective: To analyze the prognostic factors of haplo-HSCT combined with MSC in the treatment of SAA.
Methods: 127 SAA patients who had undergone haplo-HSCT with co-infusion of MSC in our center from January 2014 to August 2019 were analyzed retrospectively. Median age was 11 (1-37) years, and median follow-up time was 39.8 (1-74) months.
Results: The median time for neutrophil and platelet engraftment was 14 d and 18 d respectively. The cumulative incidences of grade III-IV aGVHD was 4.4%±1.9% at day +100. The 2-year cumulative incidence of extensive cGVHD was 8.3%± 2.7%. The estimated 3-year OS was 86.1%±3.1%. Univariate analysis showed that high-dose CD34+ cells (>6.69×106/kg) could promote the engraftment of neutrophil (97.9%±0.05% vs 88.6%±0.13% at day +21, P=0.0006) and platelet (81.2%±0.33% vs 70.8%±0.26% at day +28, P=0.002) and did not increase the incidence of aGVHD (10.4%±0.1% vs 18.9%±0.1% at day +100, P=0.18). More nucleated cells (>12.78×108/kg) caused a lower incidence of grade II-IV aGVHD (8.6%±0.13% vs 21.7%±0.25% at day+100, P=0.04) and a higher incidence of 3-year OS (91.3%±3.2% vs 78.1%±6.5%, P=0.03) than less nucleated cells (≤12.78×108/kg). Younger patients (age≤12 y) had faster neutrophil engraftment (94.9%±0.06% vs 87.5%±0.24% at day+21, P=0.02), higher 3-year OS (93.6%±2.8% vs 75.9%±6.4%, P=0.006) and higher 3-year FFS (93.6%±2.8% vs 68.3%±7.1%, P=0.000) than older patients (age>12 y). The shorter the time from diagnosis to HSCT (≤29.5 months), the higher the 3-year FFS of patients (88.8%±3.5% vs 74.2%±7.2%, P=0.028). Male patients with female donors had higher cumulative incidence of extensive cGVHD than others (20.0%±0.8% vs 4.6%±0.1%, P=0.01).
Conclusion: In the haplo-HSCT of SAA, the prognosis of children patients is better than that of adults patients. More CD34+ cells and nucleated cells can promote engraftment, reduce the incidence of aGVHD and improve OS. HSCT should be performed as early as possible, and the occurrence of cGVHD should be reduced in male patients by avoiding female donors.
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