Yusuf Usman, Hale Gregory A, Carr Jeanne, Gu Zhengming, Benaim Ely, Woodard Paul, Kasow Kimberly A, Horwitz Edwin M, Leung Wing, Srivastava Deo Kumar, Handgretinger Rupert, Hayden Randall T
Division of Stem Cell Transplantation, Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Transplantation. 2006 May 27;81(10):1398-404. doi: 10.1097/01.tp.0000209195.95115.8e.
Adenovirus (ADV) infections are associated with significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The virus is endemic in the general pediatric population and frequently causes severe disease in immunocompromised patients, especially children. We report our experience with cidofovir (CDV) for treatment of ADV infection in 57 HSCT patients, median age 8 years (range 0.5-26).
Peripheral blood was prospectively screened weekly on all patients for ADV by quantitative real-time PCR for the first 100 days post-HSCT or longer if clinically indicated. Cultures for viral pathogens were performed from other involved sites. Upon detection of ADV by PCR, culture or tissue histopathology, CDV was given intravenously at 5 mg/kg weekly for 2 consecutive weeks, then every 2 weeks until 3 consecutive ADV-negative samples were documented from all previously invoved sites.
The clinical manifestations of ADV infection were: diarrhea (53%), fever (21%), hemorrhagic cystitis (12%), and pneumonitis (11%). Eight patients (14%) presented with disseminated disease. CDV treatment resulted in complete resolution of clinical symptoms in 56 (98%) patients in whom the virus became undetectable by all methods. One patient died due to ADV pneumonitis. No cases of dose-limiting nephrotoxicity were observed. CONCLUSIONS. Cidofovir appeared safe and effective for the treatment of ADV infection in this predominantly pediatric HSCT population. Vigilant surveillance and early treatment with CDV can prevent the poor outcomes associated with ADV disease. A larger prospective study is needed to further determine the role of CDV in the treatment of ADV after HSCT.
腺病毒(ADV)感染与造血干细胞移植(HSCT)后的显著发病率和死亡率相关。该病毒在普通儿科人群中呈地方性流行,并且经常在免疫功能低下的患者,尤其是儿童中引起严重疾病。我们报告了我们使用西多福韦(CDV)治疗57例HSCT患者腺病毒感染的经验,这些患者的中位年龄为8岁(范围0.5 - 26岁)。
在HSCT后的前100天每周对所有患者的外周血进行前瞻性腺病毒定量实时PCR筛查,如果临床有指征则筛查更长时间。从其他受累部位进行病毒病原体培养。通过PCR、培养或组织病理学检测到腺病毒后,静脉注射CDV,剂量为5mg/kg,每周1次,连续2周,然后每2周1次,直至所有先前受累部位连续3次样本腺病毒检测呈阴性。
腺病毒感染的临床表现为:腹泻(53%)、发热(21%)、出血性膀胱炎(12%)和肺炎(11%)。8例患者(14%)出现播散性疾病。CDV治疗使56例(98%)患者的临床症状完全缓解,所有检测方法均未检测到病毒。1例患者死于腺病毒肺炎。未观察到剂量限制性肾毒性病例。结论。在这个以儿科为主的HSCT人群中,西多福韦似乎对治疗腺病毒感染安全有效。对CDV进行警惕的监测和早期治疗可预防与腺病毒疾病相关的不良后果。需要进行更大规模的前瞻性研究以进一步确定CDV在HSCT后腺病毒治疗中的作用。