Cytomegalovirus Immune reconstitution in cord blood transplant recipients on letermovir prophylaxis.

Cytomegalovirus Immune reconstitution in cord blood transplant recipients on letermovir prophylaxis.
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接受莱特莫韦预防的脐带血移植受者的巨细胞病毒免疫重建。

DOI:
10.1111/tid.14104
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发表时间:
2023
期刊:
Transplant infectious disease : an official journal of the Transplantation Society
影响因子:
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通讯作者:
Weinberg,Adriana
Weinberg,Adriana
中科院分区:
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文献类型:
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作者:
Abidi,MaheenZ;Molina,KyleC;Garth,Krystle;Gutman,JonathanA;Weinberg,Adriana

文献摘要

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简介巨细胞病毒 (CMV) 可导致脐带血移植 (CBT) 接受者显着发病和死亡。 CMV 特异性细胞介导免疫 (CMV-CMI) 的发展与防止 CMV 临床意义再激活 (CsCMV) 相关。在本研究中,我们评估了莱特莫韦预防性治疗期间的 CMV-CMI 重建,该治疗可预防 CsCMV,而不完全抑制 CMV 再激活。方法我们使用双色 CMV 特异性 IFNγ/IL2 FLUOROSpot 测量了莱特莫韦预防性治疗后+90 天后移植前以及移植后+180 和 +360 天时 CMV 血清阳性 CBT 受者的 CMV-CMI。从医疗记录中提取 CsCMV 和非 CsCMV 重新激活。 CsCMV 被定义为使用全血测定的 CMV 病毒载量≥5,000 IU/ml。结果在 70 名 CBT 接受者中,31 名参与者在第 +90 天时出现了 CMV-CMI,另外 8 名和 5 名参与者在第 +180 天和 +360 天时分别出现了 CMV-CMI。 38 名参与者出现了 CMV 重新激活,其中 9 名参与者患有 CsCMV。大多数重新激活(38 中的 33 次)发​​生在 Day+180 之前。九名患有 CsCMV 的参与者中有六人存在早期 CMV-CMI,表明缺乏针对 CsCMV 的保护。此外,第+90天的CMV-CMI强度在患有CsCMV和非CsCMV的参与者之间没有差异。结论大约50%的CBT接受者在莱特莫韦预防性治疗期间重建了CMV-CMI。然而,CMV-CMI 并未达到针对 CsCMV 的保护水平。对于 CMV 血清阳性 CBT 接受者,可以考虑将 CMV 预防延长到第 +90 天之后。
IntroductionCytomegalovirus (CMV) can cause significant morbidity and mortality in cord blood transplant (CBT) recipients. Development of CMV‐specific cell‐mediated immunity (CMV‐CMI) has been associated with protection against CMV clinically significant reactivation (CsCMV). In this study, we evaluated CMV‐CMI reconstitution during letermovir prophylactic therapy, which prevents CsCMV without complete suppression of CMV reactivation.MethodsWe measured CMV‐CMI in CMV‐seropositive CBT recipients pre‐transplant after Day+90 of letermovir prophylaxis and at Days +180, and +360‐ post‐transplant using a dual color CMV‐specific IFNγ/IL2 FLUOROSpot. CsCMV and nonCsCMV reactivations were abstracted from medical records. CsCMV was defined as CMV viral load ≥5,000 IU/ml using a whole blood assay.ResultsAmong 70 CBT recipients, 31 developed CMV‐CMI by Day+90 and an additional eight and five participants by Days +180 and +360, respectively. Thirty‐eight participants developed CMV reactivation, including nine with CsCMV. Most reactivations (33 of 38) occurred before Day+180. Early CMV‐CMI was present in six out of nine participants with CsCMV, indicating a lack of protection against CsCMV. Moreover, the magnitude of CMV‐CMI at Day+90 did not differ between participants with CsCMV and nonCsCMV.ConclusionApproximately 50% of CBT recipients reconstituted CMV‐CMI during letermovir prophylactic therapy. However, CMV‐CMI did not reach levels protective against CsCMV. Extension of CMV prophylaxis beyond Day+90 may be considered in CMV‐seropositive CBT recipients.