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
{"title":"在肺移植受者中使用 Letermovir 进行巨细胞病毒一级预防。","authors":"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","doi":"10.1111/tid.14337","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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<sup>9</sup>/L), severe leukopenia (WBC ≤ 2.0 × 10<sup>9</sup>/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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14337"},"PeriodicalIF":2.6000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.\",\"authors\":\"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\",\"doi\":\"10.1111/tid.14337\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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<sup>9</sup>/L), severe leukopenia (WBC ≤ 2.0 × 10<sup>9</sup>/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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":23318,\"journal\":{\"name\":\"Transplant Infectious Disease\",\"volume\":\" \",\"pages\":\"e14337\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplant Infectious Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/tid.14337\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplant Infectious Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/tid.14337","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/9 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.
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.
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.
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