Hematopoietic Stem Cell Transplantation and Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Hematopoietic Stem Cell Transplantation and Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California.
Transplant Cell Ther. 2023 Jun;29(6):397.e1-397.e6. doi: 10.1016/j.jtct.2023.02.022. Epub 2023 Mar 4.
Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients.
人疱疹病毒 6（HHV-6）在异基因造血干细胞移植（allo-HSCT）后常会再激活，与更高的死亡率和增加的移植相关并发症相关。我们假设，在血浆 HHV-6 病毒载量的较低切点采用短疗程膦甲酸进行抢先治疗，将有效治疗早期 HHV-6 再激活，预防并发症并避免这些患者住院。我们回顾了 2020 年 5 月至 2022 年 11 月期间，在我们机构进行 allo-HSCT 后，因 HHV-6 再激活而接受每日一次膦甲酸 60 至 90mg/kg 治疗 7 天的成人（年龄≥18 岁）患者的结局。在移植后前 100 天，每月监测两次血浆 HHV-6 病毒载量，再激活后每周监测两次，直至病毒载量恢复正常。分析纳入了 11 例中位年龄为 46 岁（范围，23 至 73 岁）的患者。10 例患者采用单倍体相合供者，1 例患者采用 HLA 匹配的亲缘供者。最常见的诊断是急性白血病（9 例）。4 例患者采用清髓性和强度减低预处理方案。10 例患者接受了基于环磷酰胺的移植后移植物抗宿主病预防治疗。中位随访时间为 440 天（范围，174 至 831 天），HHV-6 再激活的中位时间为移植后 22 天（范围，15 至 89 天）。首次再激活时的中位病毒载量为 3100 拷贝/ml（范围，210 至 118000 拷贝/ml），中位峰值病毒载量为 11300 拷贝/ml（范围，600 至 983000 拷贝/ml）。所有患者均接受了膦甲酸短疗程治疗，其中 7 例接受 90mg/kg/天（n=7），4 例接受 60mg/kg/天（n=4）。所有患者在治疗 1 周完成时，血浆 HHV-6 DNA 均无法检测到。未发生 HHV-6 脑炎或肺炎。所有患者均在中位时间为 16 天（范围，8 至 22 天）和 26 天（范围，14 至 168 天）后获得中性粒细胞和血小板植入，无二次移植物失败。未发现膦甲酸治疗相关的并发症。1 例 HHV-6 病毒载量极高的患者出现复发再激活，接受了第二疗程膦甲酸作为门诊治疗。每日一次膦甲酸短疗程治疗可有效治疗移植后早期 HHV-6 再激活，并可能降低 HHV-6 相关和治疗相关并发症的发生率，并避免这些患者住院。
