Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.

IF 2.6 4区医学 Q3 IMMUNOLOGY Transplant Infectious Disease Pub Date : 2024-10-01 Epub Date: 2024-07-09 DOI:10.1111/tid.14337

Hanna L Kleiboeker, Jacob Wang, Nicole Borkowski, Brad Miner, Alyson Prom, Krista Paplaczyk, 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 a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV).

Methods: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 10⁹/L), severe leukopenia (WBC ≤ 2.0 × 10⁹/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection.

Results: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance.

Conclusions: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.

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在肺移植受者中使用 Letermovir 进行巨细胞病毒一级预防。

背景：巨细胞病毒（CMV）是肺移植（LTX）后不良结局的驱动因素，而使用缬更昔洛韦（VGC）进行一级预防（PPX）是标准治疗方法。缬更昔洛韦（VGC）与骨髓抑制有关，因此人们对来特莫韦（LTV）产生了兴趣：评估对象为2015年4月1日至2022年7月30日期间在我院接受LTX治疗的成人。如果CMV风险较低（D-/R-）、存活率为9/L）、严重白细胞减少（WBC ≤ 2.0 × 109/L）和中性粒细胞减少（绝对中性粒细胞计数≤ 1500 cells/µL）需要使用粒细胞集落刺激因子（GCSF）进行PPX治疗，则排除患者。次要结果包括突破性 CMV 感染和 PPX 后 CMV 感染：结果：204 名患者符合纳入标准：175 名患者接受 VGC，29 名患者接受 LTV（VGC 转换后）。大多数患者接受了双侧 LTX（62.7%），非淋巴细胞耗竭诱导（96.6%）和中度风险血清状态（D+/R+，48.5%）。患者在移植后平均 178 天（标准差 80.8 天）后从 VGC 过渡到 LTV。使用 VGC 的患者出现白细胞减少症（82.3% 对 58.6%，p = 0.008）、严重白细胞减少症（57.1% 对 31.0%，p = 0.016）和需要 GCSF 的中性粒细胞减少症（70.9% 对 51.7%，p = 0.048）的比例明显更高。突破性感染（5.7% vs. 3.4%，p = 0.955）和PPX后感染（24.6% vs. 37.9%，p = 0.199）情况相似。对高危血清状态患者进行的亚组分析显示了类似的趋势，但未达到统计学意义：在这项单中心研究中，与 VGC 相比，LTV 降低了需要 GCSF 的白细胞减少症和中性粒细胞减少症的发生率。突破性感染和PPX后感染没有明显差异。这些证据表明，在LTX受者中，与VGC相比，LTV的疗效相当，且骨髓抑制减少，可作为PPX的适当替代方案。

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来源期刊

Transplant Infectious Disease 医学-传染病学

CiteScore

5.30

自引率

7.70%

发文量

210

审稿时长

4-8 weeks

期刊介绍： Transplant Infectious Disease has been established as a forum for presenting the most current information on the prevention and treatment of infection complicating organ and bone marrow transplantation. The point of view of the journal is that infection and allograft rejection (or graft-versus-host disease) are closely intertwined, and that advances in one area will have immediate consequences on the other. The interaction of the transplant recipient with potential microbial invaders, the impact of immunosuppressive strategies on this interaction, and the effects of cytokines, growth factors, and chemokines liberated during the course of infections, rejection, or graft-versus-host disease are central to the interests and mission of this journal. Transplant Infectious Disease is aimed at disseminating the latest information relevant to the infectious disease complications of transplantation to clinicians and scientists involved in bone marrow, kidney, liver, heart, lung, intestinal, and pancreatic transplantation. The infectious disease consequences and concerns regarding innovative transplant strategies, from novel immunosuppressive agents to xenotransplantation, are very much a concern of this journal. In addition, this journal feels a particular responsibility to inform primary care practitioners in the community, who increasingly are sharing the responsibility for the care of these patients, of the special considerations regarding the prevention and treatment of infection in transplant recipients. As exemplified by the international editorial board, articles are sought throughout the world that address both general issues and those of a more restricted geographic import.