De Novo Letermovir for Cytomegalovirus Prophylaxis in High-Risk Liver Transplant Recipients

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2025-04-28 DOI:10.1111/ctr.70169

Hanna L. Kleiboeker, Jillian L. Descourouez, Chris M. Saddler, David Al-Adra, John P. Rice, Margaret R. Jorgenson

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引用次数: 0

Abstract

Background

Cytomegalovirus (CMV) drives negative outcomes after liver transplant (LT), with patients having high-risk serostatuses (D+/R−) being especially vulnerable. While valganciclovir (VGC) remains the standard-of-care, letermovir (LTV) represents a promising potential in LT, given the reduced myelosuppression.

Methods

Adult patients receiving an LT with high-risk CMV serostatus (D+/R−) June 1, 2021–June 6, 2024 were evaluated. Patients were included in the standard-of-care (SOC) or LTV cohort based on de novo antiviral prophylaxis regimen. The primary objective was the safety and tolerability of VGC compared to LTV.

Results

Sixty-one patients met inclusion criteria: 35 in SOC and 26 in LTV cohorts. A significantly higher proportion of patients in the LTV cohort completed antiviral prophylaxis (28.6% vs. 80.8%, p < 0.001), with most patients in the SOC cohort experiencing VGC intolerance (71.4%). No patients terminated LTV due to intolerance or breakthrough. Patients in the SOC cohort had lower white blood cell (1.6 vs. 2.75 × 10³ cells/mm3; p < 0.001) and absolute neutrophil (850 vs. 2260 cells/µL p = 0.003) nadir at 6 months. Significantly more patients in the SOC cohort required granulocyte-colony stimulating factor (57.1% vs. 15.4%, p < 0.001). Patients in the LTV cohort tolerated significantly higher doses of mycophenolate through 12 months post-transplant.

Conclusion

De novo LTV for primary prophylaxis after LT appears to be safe and effective. LTV is more likely to be successfully completed than the current SOC and is associated with less myelosuppressive toxicity, which allows maintenance of higher mycophenolate doses. Future studies are needed to evaluate the impact of LTV on rejection rates and transplant outcomes.

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新雷替莫用于高危肝移植受者巨细胞病毒预防

巨细胞病毒（CMV）会导致肝移植（LT）后的负面结果，高危血清状态（D+/R−）的患者尤其容易受到感染。虽然缬更昔洛韦（VGC）仍然是标准治疗，但考虑到减少骨髓抑制，莱特莫韦（LTV）在LT中具有很好的潜力。方法对2021年6月1日至2024年6月6日接受肝移植的CMV高危血清状态（D+/R−）的成人患者进行评估。患者被纳入基于新抗病毒预防方案的标准护理（SOC）或LTV队列。主要目标是VGC相对于LTV的安全性和耐受性。结果61例患者符合纳入标准：SOC组35例，LTV组26例。LTV队列中完成抗病毒预防治疗的患者比例显著较高(28.6% vs. 80.8%, p <；0.001)，大多数SOC队列患者出现VGC不耐受（71.4%）。无患者因不耐受或突破终止LTV。SOC组患者的白细胞较低(1.6 vs. 2.75 × 103细胞/mm3；p & lt;绝对中性粒细胞（850 vs 2260细胞/µL p = 0.003）在6个月时达到最低点。SOC队列中需要粒细胞集落刺激因子的患者明显更多(57.1% vs 15.4%, p <；0.001)。LTV组患者在移植后12个月内耐受更高剂量的霉酚酸盐。结论肝移植后重新进行LTV一级预防是安全有效的。与目前的SOC相比，LTV更有可能成功完成，并且与较少的骨髓抑制毒性相关，这允许维持较高的霉酚酸盐剂量。未来的研究需要评估LTV对排异率和移植结果的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.