血液病患者异基因造血干细胞移植后粒细胞植入前死亡原因分析

Causes and characteristics of pre-engraftment mortality after allogeneic hematopoietic stem cell transplantation

目的:分析异基因造血干细胞移植(allo-HSCT)患者粒细胞植入前死亡原因及人群特征。方法:对2016年1月至2023年7月在北京大学人民医院行allo-HSCT的全部7427例患者进行回顾性分析。结果:7427例患者中有56例(0.75%)在中性粒细胞植入前死亡,中位死亡时间为+7 d(-3 d~+38 d)。急性白血病(AL)、重型再生障碍性贫血(SAA)、骨髓增生异常综合征(MDS)患者的中位死亡时间分别为+11 d(-1 d~+38 d)、+3 d(-1 d~+34 d)、+16 d(-1 d~38 d)(P=0.013)。主要死亡原因为感染(39.3%)、预处理心脏毒性(28.6%)和颅内出血(26.8%)。感染是引起AL和MDS患者最常见的死亡原因(55.0%、60.0%)。预处理心脏毒性所致死亡主要见于SAA患者(71.4%),而在AL患者中未见到,MDS中仅1例。53.3%的颅内出血死亡患者合并严重感染。感染、预处理心脏毒性、颅内出血引起植入前死亡的中位时间分别是+11 d(-1 d~+38 d)、+2.5 d(-1 d~+17 d)、+8 d(-3 d~+37 d)(P<0.001)。结论:感染是allo-HSCT患者粒细胞植入前死亡的主要原因,SAA患者应关注严重心脏毒性导致的植入前死亡。

Objective To analyze the causes and demographic characteristics of pre-engraftment mortality in patients who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)and investigate the risk factors and measures for preventing pre-engraftment mortality.Methods A retrospective case analysis,involving a total of 7427 patients who underwent allo-HSCT at Peking University People’s Hospital between January 2016 and July 2023,was conducted.Results Among the 7427 patients who underwent allo-HSCT,56 cases(0.75%)experienced pre-engraftment mortality.The median time to death for these 56 patients was+7(-3 to+38)days after stem cell infusion.The median times to death for patients with acute leukemia(AL),severe aplastic anemia(SAA),and myelodysplastic syndrome(MDS)were+11(-1 to+38),+3(-1 to+34),and+16(-1 to+38)days,respectively(P=0.013).The main causes of pre-engraftment mortality were infection(39.3%),cardiac toxicity(28.6%),and intracranial hemorrhage(26.8%).Infection was the most common cause of pre-engraftment mortality in patients with AL and MDS(55.0%and 60.0%),whereas cardiac toxicity was predominantly observed in patients with SAA(71.4%),with no cases in patients with AL and only one case in patients with MDS.Among patients who died from intracranial hemorrhage,53.3%had severe infections.The median times to death for infection,cardiac toxicity,and intracranial hemorrhage was+11(-1 to+38),+2.5(-1 to+17),and+8(-3 to+37)days,respectively(P<0.001).Conclusions Infection is the primary cause of pre-engraftment mortality in allo-HSCT,and severe cardiac toxicity leading to pre-engraftment mortality should be closely monitored in patients with SAA.