Abstract:
Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Management of refractory CMV infections, especially in developing countries, can be challenging due to the limited availability of second and third-line antiviral drugs or alternative treatments. Here, we present a case of an 8 years-old patient diagnosed with acute myeloid leukemia. Eight months post-diagnosis, the patient underwent TCR-αβ+/CD19+-depleted haploidentical HSCT. Both the donor and recipient tested positive for anti-CMV IgG and negative for IgM antibodies. Before transplantation, the patient received CMV prophylaxis in the form of intravenous ganciclovir. Post-transplantation, the patient exhibited oscillating CMV viral loads and was diagnosed with a refractory infection. Treatment with ganciclovir, foscarnet, and cidofovir was unsuccessful. Sequencing of UL-54 and UL-97 genes was performed to rule out potential resistance to first-line treatment. Ten months after the HSCT, the child died from hypovolemic shock due to gastrointestinal bleeding. This is the first case reported in Peru and Latin America of a refractory CMV infection in a pediatric HSCT recipient without evidence of clinical symptoms and CMV genetic resistance. This case demonstrates the need for alternative treatments to manage refractory CMV infections, especially in haploidentical HSCT cases where drug resistance is frequent (~15%). Furthermore, this case highlights the importance of using highly sensitive genetic tools to detect mutations associated with virus resistance in a broader range of the viral genome.
摘要:
巨细胞病毒(CMV)感染是造血干细胞移植(HSCT)患者的常见并发症。难治性CMV感染的管理,特别是在发展中国家,由于二线和三线抗病毒药物或替代疗法的可用性有限,这可能是具有挑战性的。这里,我们介绍一例8岁的急性髓系白血病患者.诊断后八个月,患者接受TCR-αβ+/CD19+单倍体相合HSCT.供者和受者的抗CMVIgG检测为阳性,IgM抗体检测为阴性。移植前,患者接受静脉注射更昔洛韦形式的CMV预防.移植后,患者出现CMV病毒载量振荡,并被诊断为难治性感染.用更昔洛韦治疗,Foscarnet,和西多福韦不成功。对UL-54和UL-97基因进行测序以排除对一线治疗的潜在抗性。HSCT10个月后,这个孩子死于胃肠道出血导致的低血容量性休克。这是秘鲁和拉丁美洲报道的第一例儿童HSCT受者难治性CMV感染的病例,没有临床症状和CMV遗传抗性的证据。此病例表明需要替代疗法来管理难治性CMV感染,特别是在耐药频繁的单倍体HSCT病例中(〜15%)。此外,这一案例凸显了使用高度敏感的遗传工具在更广泛的病毒基因组中检测与病毒抗性相关的突变的重要性.