Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Transplant Cell Ther. 2021 Oct;27(10):866.e1-866.e9. doi: 10.1016/j.jtct.2021.07.001. Epub 2021 Jul 10.
Transfusion therapy is a critical part of supportive care early after allogeneic hematopoietic cell transplantation (allo-HCT). Platelet and RBC transfusions elicit immunomodulatory effects in the recipient, but if this impacts the risk of acute graft-versus-host disease (aGVHD) has only been scarcely investigated. We investigated if platelet and RBC transfusions were associated with the development of aGVHD following myeloablative allo-HCT in a cohort of 664 patients who underwent transplantation between 2000 and 2019. Data were further analyzed for the impact of blood donor age and sex and blood product storage time. Exploratory analyses were conducted to assess correlations between transfusion burden and plasma biomarkers of inflammation and endothelial activation and damage. Between day 0 and day +13, each patient received a median of 7 (IQR, 5 to 10) platelet transfusions and 3 (IQR, 2 to 6) RBC transfusions (Spearman's ρ = 0.49). The cumulative sums of platelet and RBC transfusions, respectively, received from day 0 to day +13 were associated with subsequent grade II-IV aGVHD in multivariable landmark Cox models (platelets: adjusted hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.06 to 1.51; RBCs: adjusted HR, 1.41; 95% CI, 1.09 to 1.82; both per 5 units; 184 events). For both platelet and RBC transfusions, we did not find support for a difference in the risk of aGVHD according to age or sex of the blood donor. Transfusion of RBCs with a storage time longer than the median of 8 days was inversely associated with aGVHD (HR per 5 units, 0.54; 95% CI, 0.30 to 0.96); however, when using an RBC storage time of ≥14 days as a cutoff, there was no longer evidence for an association with aGVHD (HR, 1.03 per 5 units; 95% CI, 0.53 to 2.00). For platelets, there was no clear association between storage time and the risk of aGVHD. The transfusion burdens of platelets and RBCs were positively correlated with plasma levels of TNF-α, IL-6, and soluble thrombomodulin at day +14. In conclusion, platelet and RBC transfusions in the first 2 weeks after myeloablative allo-HCT were associated with subsequent development of grade II-IV aGVHD. We did not find evidence of an impact of blood donor age or sex or blood product storage time on the risk of aGVHD. Our findings support restrictive transfusion strategies in allo-HCT recipients.
输血治疗是异基因造血细胞移植（allo-HCT）后支持治疗的重要组成部分。血小板和红细胞输注在受者中引起免疫调节作用，但如果这会影响急性移植物抗宿主病（aGVHD）的风险，目前还鲜有研究。我们研究了在 2000 年至 2019 年间接受移植的 664 例接受清髓性 allo-HCT 的患者队列中，血小板和红细胞输注是否与 aGVHD 的发生有关。进一步分析了血液供体年龄和性别以及血液制品储存时间对其的影响。进行了探索性分析，以评估输血负担与炎症和内皮激活和损伤的血浆生物标志物之间的相关性。在第 0 天至第+13 天之间，每位患者接受了中位数为 7（IQR，5 至 10）次血小板输注和 3（IQR，2 至 6）次红细胞输注（Spearman's ρ=0.49）。从第 0 天到第+13 天输注的血小板和红细胞的累积总和，在多变量 landmark Cox 模型中与随后发生的 II-IV 级 aGVHD 相关（血小板：校正后的危险比[HR]，1.27；95%置信区间[CI]，1.06 至 1.51；RBC：校正 HR，1.41；95%CI，1.09 至 1.82；每 5 个单位；184 个事件）。对于血小板和红细胞输注，我们没有发现根据血液供体的年龄或性别输血与 aGVHD 风险之间存在差异的证据。输注储存时间长于中位数 8 天的 RBC 与 aGVHD 呈负相关（每 5 个单位 HR，0.54；95%CI，0.30 至 0.96）；然而，当使用 RBC 储存时间≥14 天作为截止值时，与 aGVHD 之间不再存在关联（HR，每 5 个单位 1.03；95%CI，0.53 至 2.00）。对于血小板，储存时间与 aGVHD 风险之间没有明确的关联。血小板和 RBC 输注负担与第+14 天的 TNF-α、IL-6 和可溶性血栓调节蛋白的血浆水平呈正相关。总之，清髓性 allo-HCT 后 2 周内的血小板和 RBC 输注与随后发生的 II-IV 级 aGVHD 有关。我们没有发现血液供体年龄或性别或血液制品储存时间对 aGVHD 风险的影响的证据。我们的发现支持 allo-HCT 受者的限制性输血策略。
