Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA.
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Transpl Infect Dis. 2024 Oct;26(5):e14337. doi: 10.1111/tid.14337. Epub 2024 Jul 9.
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).
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 × 10/L), severe leukopenia (WBC ≤ 2.0 × 10/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.
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.
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.
巨细胞病毒（CMV）是肺移植（LTX）后不良结局的驱动因素，缬更昔洛韦（VGC）的预防性用药（PPX）是标准治疗方法。VGC 与骨髓抑制有关，这促使人们对乐特韦（LTV）产生了兴趣。
评估了 2015 年 4 月 1 日至 2022 年 7 月 30 日期间在我们机构接受 LTX 的成年人。如果患者的 CMV 风险较低（D-/R-）、LTX 后存活时间<90 天或在 PPX 停药前转院，将被排除在外。主要结局是白细胞减少症（白细胞计数[WBC]≤3.0×10/L）、严重白细胞减少症（WBC≤2.0×10/L）和中性粒细胞减少症（绝对中性粒细胞计数≤1500 个/µL），需要在 PPX 时使用粒细胞集落刺激因子（GCSF）。次要结局包括突破性 CMV 感染和 PPX 后 CMV 感染。
204 名患者符合纳入标准：175 名患者接受 VGC 治疗，29 名患者接受 LTV 治疗（VGC 转换后）。大多数患者接受了双侧 LTX（62.7%），采用非淋巴细胞耗竭诱导（96.6%）和中度风险血清学状态（D+/R+，48.5%）。患者在移植后平均 178 天（SD 80.8 天）时从 VGC 转为 LTV。接受 VGC 的患者发生白细胞减少症（82.3%比 58.6%，p=0.008）、严重白细胞减少症（57.1%比 31.0%，p=0.016）和中性粒细胞减少症需要 GCSF（70.9%比 51.7%，p=0.048）的情况明显更多。突破性（5.7%比 3.4%，p=0.955）和 PPX 后（24.6%比 37.9%，p=0.199）感染情况相似。高风险血清学状态患者的亚组分析显示出类似的趋势，但未达到统计学意义。
在这项单中心研究中，与 VGC 相比，LTV 可降低白细胞减少症和中性粒细胞减少症需要 GCSF 的发生率。突破性和 PPX 后感染无显著差异。这些证据表明，LTV 在 LTX 受者中与 VGC 相比具有相似的疗效，且骨髓抑制作用更低，可能是 PPX 的一种合适替代方案。
