Comparison of frontline immunosuppressive therapy and hematopoietic stem cell transplantation for severe hepatitis-associated aplastic anemia
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摘要: 目的 比较一线免疫抑制治疗(immunosuppressive therapy，IST)及造血干细胞移植(hematopoietic stem cell transplantation，HSCT)治疗肝炎相关性再生障碍性贫血(hepatitis-associated aplastic anemia，HAAA)的疗效。方法 选择2013年1月1日至2022年8月31日诊断为重度或极重度HAAA的患者41例，进行一线IST(12例)或HSCT治疗(29例)，其中同胞全相合供者异基因造血干细胞移植(matched-sibling donor hematopoietic stem cell transplantation，MSD-HSCT)13例，单倍体异基因造血干细胞移植(haplo-identical donor hematopoietic stem cell transplantation，HID-HSCT)16例。结果 除死亡事件外，所有患者移植后中位随访时间为67(16~129)个月。MSD-HSCT组和HID-HSCT组患者造血重建时间、感染发生率、Ⅱ~Ⅳ度急性移植物抗宿主病、慢性移植物抗宿主病发生率差异均无统计学意义。IST组治疗失败率明显高于HSCT组(41.7% vs 10.3%，P=0.034)。整个队列显示5年总生存率(overall survival，OS)和无失败生存率(failure-free survival，FFS)分别为85.4%和80.5%。MSD-HSCT组、HID-HSCT组、IST组5年OS率分别为92.3%、87.5%和75.0%，5年FFS率分别为92.3%、87.5%和58.3%。HSCT组和IST组5年OS率差异无统计学意义；MSD-HSCT组5年FFS率较IST组明显延长(P=0.039)；MSD-HSCT组和HID-HSCT组5年OS率及FFS率差异均无统计学意义。结论 HSCT较IST更适合于极重型或爆发性HAAA患者。MSD-HSCT仍是HAAA治疗的一线选择，对于没有MSD供者的年轻患者来说，HID-HSCT可以替代IST作为一线选择。
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关键词:
- 肝炎相关再生障碍性贫血 /
- 异基因造血干细胞移植 /
- 免疫抑制治疗
Abstract: Objective To compare the clinical efficacy between frontline immunosuppressive therapy(IST) and hematopoietic stem cell transplantation(HSCT) for patients with severe hepatitis-associated aplastic anemia(HAAA).Methods A total of 41 patients who received frontline IST(12 cases) or HSCT(29 cases) between January 1, 2013 and August 31, 2022 were retrospectively analyzed. Among 29 patients undergoing HSCT, there were 13 cases of matched-sibling donor hematopoietic stem cell transplantation(MSD-HSCT) and 16 cases of haplo-identical donor hematopoietic stem cell transplantation(HID-HSCT).Results Except for death events, the median follow-up time for all patients after transplantation was 67(16-129) months. There was no significant difference in hematopoietic reconstruction time, the infection rate, the incidences of gradeⅡ-Ⅳ acute graft-versus-host disease and chronic graft-versus-host disease between the MSD-HSCT group and the HID-HSCT group. The incidence of treatment failure in the IST group was higher than that in the HSCT group(41.7% vs 10.3%, P=0.034). The estimated 5-year overall survival(OS) and failure-free survival(FFS) were 85.4% and 80.5% for all of the 41 patients. The estimated 5-year OS in the MSD-HSCT group, HID-HSCT group and IST group were 92.3%, 87.5% and 75.0%, respectively. The estimated 5-year FFS in the MSD-HSCT group, HID-HSCT group and IST group were 92.3%, 87.5% and 58.3%, respectively. There was no significant difference in the estimated 5-year OS between the HSCT group and the IST group, but the estimated 5-year FFS in the MSD-HSCT group was significantly higher than that in the IST group(P=0.039). There was no significant difference in the expected 5-year OS and FFS between the MSD-HSCT group and the HID-HSCT group.Conclusion HSCT is more suitable for patients with severe HAAA than IST. MSD-HSCT remains the first-line option for HAAA, and HID-HSCT can replace IST as the first-line option for younger patients without a MSD donor. The frontline haplo-HSCT was an effective and safe approach for the treatment of patients with SAA who lack a HLA-matched sibling donor. -
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表 1 IST组和HSCT组患者基本临床资料比较
项目 IST组
(12例)HSCT组
(29例)P 年龄/岁 24(11~57) 26(19~43) 0.58 男∶女/例 8∶4 18∶11 0.54 ECOG评分0~1/例(%) 9(75.0) 23(79.3) 0.53 肝炎到AA诊断时间/月 4(2~7) 4(1.5~6) 0.41 AA诊断至治疗时间/d 7(1~14) 31(16~57) 0.39 治疗前感染/例(%) 5(41.7) 22(75.9) 0.04 肝功能(峰值) 谷丙转氨酶/(U/L) 1 432±692 1 687±812 0.45 谷草转氨酶/(U/L) 1 038±609 986±589 0.38 总胆红素/(μmol/L) 168±79 171±91 0.21 疾病状态/例(%) < 0.01 SAA 10(83.3) 3(10.3) VSAA 2(16.7) 26(89.7) 
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表 2 MSD-HSCT组和HID-HSCT组患者的基本临床资料及疗效
项目 MSD-HSCT
(13例)HID-HSCT
(16例)P 年龄/岁 27(21~43) 25(19~39) 0.41 男∶女/例 8∶5 10∶6 0.63 HCT-CT评分0~1分/例(%) 12(92.3) 14(87.5) 0.58 疾病状态/例(%) 0.42 SAA 2(15.4) 1(6.2) VSAA 11(84.6) 15(93.8) 确诊至移植时间/d 29(16~41) 24(19~57) 0.37 供-受者性别匹配/例(%) 0.39 男-男 5(38.5) 6(37.5) 男-女 3(23.1) 3(18.8) 女-女 2(15.4) 3(18.8) 女-男 3(23.1) 4(25.0) 预处理方案/例(%) 0.43 Flu/Cy+ATG 7(53.8) 7(43.8) Bu/Cy+ATG 6(46.2) 9(56.2) 造血植入时间/d 中性粒细胞植入 13(10~17) 14(10~18) 0.38 血小板植入 14(9~21) 15(11~19) 0.30 移植后1个月完全植入/例(%) 13(100.0) 16(100.0) 原发病植入失败/例(%) 0 0 Ⅱ~Ⅳ度急性GVHD/例(%) 6(46.2) 10(62.5) 0.31 慢性GVHD/例(%) 1(7.7) 3(18.8) 0.38 感染/例(%) 细菌/真菌 9(69.2) 14(87.5) 0.23 CMV 5(38.5) 11(68.8) 0.63 EBV 3(23.1) 5(31.3) 0.51 PTLD/例(%) 1(7.7) 2(12.5) 0.58 死亡/例(%) 1(7.7) 2(12.5) 0.58 感染 0 1(6.3) GVHD 0 1(6.3) 其他 1(7.7) 0
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