低剂量抗胸腺细胞球蛋白联合移植后环磷酰胺对急性白血病造血干细胞移植后的影响  

Low-dose antithymocyte globulin with post-transplantation cyclophosphamide decreases early relapse post hematopoietic stem cell transplantation in pediatric acute leukemia

作　　者：胡梦泽[1] 胡涛[1] 李君惠[1] 张朝霞[1] 冯顺乔[1] 宋泽亮[1] 玄立田 刘嵘[1] Hu Mengze;Hu Tao;Li Junhui;Zhang Zhaoxia;Feng Shunqiao;Song Zeliang;Xuan Litian;Liu Rong(Department of Hematology,Children’s Hospital Affi liated to Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院血液科,北京100020

出　　处：《中国医刊》2025年第1期79-84,共6页Chinese Journal of Medicine

摘　　要：目的分析低剂量抗胸腺细胞球蛋白(ATG)联合移植后环磷酰胺(PTCy)对儿童急性白血病亲缘单倍体造血干细胞移植(HSCT)预后的影响。方法回顾性选取2016年1月至2022年8月在首都儿科研究所附属儿童医院接受亲缘单倍体HSCT的35例急性白血病患儿,采用减低强度预处理,使用ATG联合PTCy预防移植物抗宿主病(GVHD)。所有患儿根据ATG剂量高低分为低剂量ATG组(总剂量2.5~5.0 mg/kg,n=15)和高剂量ATG组(总剂量7.5~10.0 mg/kg,n=20)。分析两组患儿急慢性GVHD、造血植入、巨细胞病毒(CMV)和EB病毒(EBV)活化、总体生存、复发、无白血病生存(LFS)、无GVHD/无复发生存(GRFS)和非复发死亡(NRM)的差异,并进行生存分析。结果两组患儿的急性GVHD、Ⅱ~Ⅳ级急性GVHD、Ⅲ~Ⅳ级急性GVHD、慢性GVHD发生率以及中性粒细胞植入时间和血小板植入时间、CMV和EBV活化率、总体生存率、LFS、复发率、GRFS、NRM比较差异均无统计学意义(P>0.05)。进一步Kaplan-Meier生存曲线分析显示,高剂量ATG组移植后1年内的复发率高于低剂量ATG组,差异有统计学意义(P<0.05)。单因素Cox回归分析显示,移植后复发是影响生存的危险因素(P<0.05);多因素Cox回归分析显示,移植后复发和移植前疾病状态是影响生存的危险因素(P<0.05)。结论低剂量ATG联合PTCy预防儿童急性白血病移植后GVHD,患儿移植后早期复发风险低,对GVHD的预防效果与高剂量ATG相同,有望进一步改善患儿移植后生存。Objective To analyze the prognostic effect of low-dose antithymocyte globulin(ATG)dose combined with post-transplantation cyclophosphamide(PTCy)in the prevention of graft-versus-host disease(GVHD)and haploidentical hematopoietic stem cell transplantation(haplo-HSCT)in children with acute leukemia.Method We retrospectively analyzed 35 children(<16 years)with acute leukemia who underwent haplo-HSCT with ATG+PTCy dual T-cell depletion at our center from January 2016 to August 2022.Patients were categorized into low-dose and high-dose ATG groups(2.5–5.0 mg/kg,n=15 vs.7.5–10.0 mg/kg,n=20).All the patients received a reduced intensity conditioning regimen.The differences in acute and chronic GVHD,hematopoietic engraftment,virus reactivation,overall survival(OS),relapse,leukemia-free survival(LFS),GVHD/relapse-free survival(GRFS)and non-relapse mortality(NRM)were analyzed between the two groups.Result There were no significant differences in the incidence of acute GVHD,gradeⅡtoⅣacute GVHD,gradeⅢtoⅣacute GVHD and chronic GVHD,neutrophil implantation time and platelet implantation time,CMV and EBV activation rate,OS,LFS,recurrence rate,GRFS and NRM between the two groups(P>0.05).Further Kaplan-Meier survival curve analysis showed that the recurrence rate within 1 year after transplantation in the high-dose ATG group was higher than that in the low-dose ATG group,and the difference was statistically significant(P<0.05).Univariate Cox regression analysis showed that recurrence after transplantation was a risk factor for survival(P<0.05).Multivariate Cox regression analysis showed that post-transplant recurrence and pre-transplant disease status were risk factors for survival(P<0.05).Conclusion Low-dose ATG in pediatric acute leukemia HSCT,combined with PTCy,reduces early relapse risk without increasing GVHD incidence,enhancing prognosis improvement strategies.

关 键 词：急性白血病 儿童 造血干细胞移植 抗胸腺细胞球蛋白 移植后环磷酰胺 

分 类 号：R725.5[医药卫生—儿科]