In Vivo Emergence of UL56 C325Y Cytomegalovirus Resistance to Letermovir in a Patient with Acute Myeloid Leukemia after Hematopoietic Cell Transplantation
In Vivo Emergence of UL56 C325Y Cytomegalovirus Resistance to Letermovir in a Patient with Acute Myeloid Leukemia after Hematopoietic Cell Transplantation
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DOI：
10.4084/mjhid.2019.001
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发表时间：
2019-01-01
影响因子：
3.2
通讯作者：
Hilgendorf, Inken
中科院分区：
文献类型：
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作者：
Frietsch, Jochen J.;Michel, Detlef;Hilgendorf, Inken
巨细胞病毒相关的组织侵袭性疾病与异基因造血干细胞移植(HSCT)后相当大的发病率和死亡率相关。最近，终止酶抑制剂letermovir(LMV)已被批准用于预防HSCT中CMV感染。我们在此报告一位60岁女性，在巨细胞病毒血清阴性的供者星座中接受异基因造血干细胞移植后的巨细胞病毒再激活。由于CMV病毒载量持续升高和药物相关的骨髓抑制，阻止了更昔洛韦的治疗，治疗被磷甲酸钠取代。由于肾毒性，磷甲酸钠改用LMV。患者出现皮肤移植物抗宿主病，并开始使用强的松龙。随后，尽管接受了LMV治疗，CMV病毒血症仍恶化。基因分型表明，CMV UL56末端酶C325Y突变与对LMV的高水平抗性有关。强的松龙治疗导致的长期无法控制的低水平病毒血症可能有利于耐药巨细胞病毒的选择。尽管LMV的毒性很好，但医生应该意识到出现耐药性的危险因素。
CMV associated tissue-invasive disease is associated with a considerable risk of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recently, the terminase inhibitor letermovir (LMV) has been approved for prophylaxis of CMV infection in HSCT. We hereby report a 60-year-old female experiencing CMV reactivation after HSCT in a CMV seronegative donor-constellation. Due to ongoing elevated CMV viral load and drug-associated myelosuppression, which prevented ganciclovir therapy, treatment was replaced by foscarnet. Due to nephrotoxicity, foscarnet was switched to LMV. The patient developed skin GvHD and prednisolone was started. Subsequently, CMV viremia worsened despite LMV therapy. Genotyping revealed the mutation C325Y of the CMV UL56 terminase being associated with high-level resistance against LMV. Prolonged uncontrolled low-level viremia due to prednisolone treatment may have favored the selection of drug-resistant CMV. Despite the excellent toxicity profile of LMV, physicians should be aware of risk factors for the emergence of resistance.