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入住重症监护病房的异基因造血干细胞移植受者的结局,重点关注单倍体相合移植物和序贯预处理方案:一项回顾性研究结果

Outcome of allogeneic hematopoietic stem cell transplant recipients admitted to the intensive care unit with a focus on haploidentical graft and sequential conditioning regimen: results of a retrospective study.

作者信息

Gournay Viviane, Dumas Guillaume, Lavillegrand Jean-Rémi, Hariri Geoffroy, Urbina Tomas, Baudel Jean-Luc, Ait-Oufella Hafid, Maury Eric, Brissot Eolia, Legrand Ollivier, Malard Florent, Mohty Mohamad, Guidet Bertrand, Duléry Rémy, Bigé Naïke

机构信息

Service de Médecine Intensive Réanimation, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, AP-HP, 184 rue du Faubourg Saint-Antoine, 75571, Paris, Cedex 12, France.

Sorbonne Université, Université Pierre et Marie Curie, 75006, Paris, France.

出版信息

Ann Hematol. 2021 Nov;100(11):2787-2797. doi: 10.1007/s00277-021-04640-7. Epub 2021 Sep 3.

Abstract

Haploidentical transplantation has extended the availability of allogeneic hematopoietic stem cell transplant (alloHCT) to almost all patients. Sequential conditioning regimens have been proposed for the treatment of hematological active disease. Whether these new transplantation procedures affect the prognosis of critically ill alloHCT recipients remains unknown. We evaluated this question in a retrospective study including consecutive alloHCT patients admitted to the intensive care unit of a tertiary academic center from 2010 to 2017. During the study period, 412 alloHCTs were performed and 110 (27%) patients-median age 55 (36-64) years-were admitted to ICU in a median time of 58.5 (14-245) days after alloHCT. Twenty-nine (26%) patients had received a haploidentical graft and 34 (31%) a sequential conditioning. Median SOFA score was 9 (6-11). Invasive mechanical ventilation (MV) was required in 61 (55%) patients. Fifty-six (51%) patients died in the hospital. Independent factors associated with in-hospital mortality were as follows: MV (OR=8.44 [95% CI 3.30-23.19], p<0.001), delta SOFA between day 3 and day 1 (OR=1.60 [95% CI 1.31-2.05], p<0.0001), and sequential conditioning (OR=3.7 [95% CI 1.14-12.92], p=0.033). Sequential conditioning was also independently associated with decreased overall survival (HR=1.86 [95% CI 1.05-3.31], p=0.03). Other independent factors associated with reduced overall survival were HCT-specific comorbidity index ≥2 (HR=1.76 [95% CI 1.10-2.84], p=0.02), acute GVHD grade ≥2 (HR=1.88 [95% CI 1.14-3.10], p=0.01), MV (HR=2.37 [95% CI 1.38-4.07, p=0.002), and vasopressors (HR=2.21 [95% CI 1.38-3.54], p=0.001). Haploidentical transplantation did not affect outcome. Larger multicenter studies are warranted to confirm these results.

摘要

单倍体相合移植已将异基因造血干细胞移植(alloHCT)的适用范围扩大到几乎所有患者。已提出序贯预处理方案用于治疗血液系统活动性疾病。这些新的移植程序是否会影响重症alloHCT受者的预后仍不清楚。我们在一项回顾性研究中评估了这个问题,该研究纳入了2010年至2017年在一家三级学术中心重症监护病房接受连续alloHCT的患者。在研究期间,共进行了412例alloHCT,110例(27%)患者——中位年龄55岁(36 - 64岁)——在alloHCT后中位58.5天(14 - 245天)入住ICU。29例(26%)患者接受了单倍体相合移植,34例(31%)接受了序贯预处理。中位序贯器官衰竭评估(SOFA)评分是9分(6 - 11分)。61例(55%)患者需要有创机械通气(MV)。56例(51%)患者在医院死亡。与院内死亡相关的独立因素如下:MV(比值比[OR]=8.44[95%置信区间(CI)3.30 - 23.19],p<0.001),第3天和第1天的SOFA差值(OR=1.60[95%CI 1.31 - 2.05],p<0.0001),以及序贯预处理(OR=3.7[95%CI 1.14 - 12.92],p=0.033)。序贯预处理还与总生存率降低独立相关(风险比[HR]=1.86[95%CI 1.05 - 3.31],p=0.03)。与总生存率降低相关的其他独立因素包括HCT特异性合并症指数≥2(HR=1.76[95%CI 1.10 - 2.84],p=0.02),急性移植物抗宿主病(GVHD)≥2级(HR=1.88[95%CI 1.14 - 3.10],p=0.01),MV(HR=2.37[95%CI 1.38 - 4.07,p=0.002]),以及血管加压药(HR=2.21[95%CI 1.38 - 3.54],p=0.001)。单倍体相合移植不影响预后。需要更大规模的多中心研究来证实这些结果。

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