Impact of Letermovir for Cytomegalovirus Primary Prophylaxis on Myelosuppression and Immunosuppression in Lung Transplant Recipients

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2024-11-27 DOI:10.1111/ctr.70033

Hanna L. Kleiboeker, Alyson Prom, Krista Paplaczyk, Jacob Wang, Nicole Borkowski, Brad Miner, Jennifer Wright, Mrinalini Venkata Subramani, Ambalavanan Arunachalam, Alan D. Betensley, Rade Tomic, Catherine N. Myers

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引用次数: 0

Abstract

Background

Cytomegalovirus (CMV) is associated with detrimental outcomes after lung transplantation (LTX); primary prophylaxis (PPX) with valganciclovir (VGC) is guideline-recommended. VGC is associated with myelosuppression, spurring interest in letermovir (LTV).

Methods

Adults undergoing LTX between January 1, 2021, and July 30, 2022 at our institution who were converted from VGC to LTV for PPX were evaluated. Outcomes included antimetabolite dosing during PPX, the incidence and frequency of myelosuppressive events, and the time to the first myelosuppressive event.

Results

Twenty-nine LTX recipients met the inclusion criteria. Most patients received non-lymphocyte-depleting induction (96.6%) and had moderate risk CMV serostatus (D+/R+, 48.3%). Patients transitioned from VGC to LTV 177 days (IQR 102 days) post-transplant. After conversion to LTV, patients tolerated higher daily doses of mycophenolate (721 mg vs. 1000 mg, p = 0.008) or azathioprine (33.3 mg vs. 62.5 mg, p = 0.478). The incidence of myelosuppressive events was reduced (100.0% vs. 62.1%, p < 0.001) including leukopenia (96.6% vs. 58.6%, p = 0.001), severe leukopenia (82.8% vs 31.0%, p < 0.001) and neutropenia requiring GCSF (96.6% vs. 48.3%, p < 0.001) while on VGC compared to LTV. While on LTV, patients had a reduced rate of myelosuppressive events compared to VGC (1 event per 6.2 patient days vs. 1 event per 14.7 patient days, p < 0.001). While on LTV, one patient had breakthrough viremia (3.4%) that was treated with (val)ganciclovir.

Conclusions

In this single-center study, patients tolerated higher doses of antimetabolite immunosuppression, and the incidence and frequency of myelosuppressive events were reduced while on LTV compared to VGC. This evidence expands upon the current literature demonstrating improved tolerability of LTV in LTX recipients.

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用于巨细胞病毒一级预防的来替莫韦对肺移植受者骨髓抑制和免疫抑制的影响

背景：巨细胞病毒（CMV）与肺移植（LTX）后的不良预后有关；指南推荐使用缬更昔洛韦（VGC）进行一级预防（PPX）。缬更昔洛韦（VGC）与骨髓抑制有关，激发了人们对来特莫韦（LTV）的兴趣：方法：对我院 2021 年 1 月 1 日至 2022 年 7 月 30 日期间接受 LTX 治疗的成人进行了评估，他们因 PPX 而从 VGC 转为 LTV。结果包括 PPX 期间的抗代谢药物剂量、骨髓抑制事件的发生率和频率以及发生首次骨髓抑制事件的时间：29名LTX受者符合纳入标准。大多数患者接受了非淋巴细胞消耗诱导（96.6%），CMV血清状态为中度风险（D+/R+，48.3%）。患者在移植后 177 天（IQR 102 天）从 VGC 转为 LTV。转为LTV后，患者可耐受更高的霉酚酸盐（721毫克对1000毫克，p = 0.008）或硫唑嘌呤（33.3毫克对62.5毫克，p = 0.478）日剂量。与LTV相比，服用VGC时骨髓抑制事件的发生率降低（100.0% vs. 62.1%，p < 0.001），包括白细胞减少症（96.6% vs. 58.6%，p = 0.001）、严重白细胞减少症（82.8% vs. 31.0%，p < 0.001）和需要使用GCSF的中性粒细胞减少症（96.6% vs. 48.3%，p < 0.001）。与VGC相比，患者在LTV期间发生骨髓抑制事件的比率有所降低（每6.2个患者日发生1起事件 vs. 每14.7个患者日发生1起事件，p < 0.001）。在接受LTV治疗期间，一名患者出现了突破性病毒血症（3.4%），并接受了(val)更昔洛韦治疗：在这项单中心研究中，患者可以耐受更大剂量的抗代谢物免疫抑制，与VGC相比，服用LTV时骨髓抑制事件的发生率和频率均有所降低。现有文献显示，LTX受者对LTV的耐受性有所改善，这一证据进一步证实了这一点。

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.