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用西多福韦治疗干细胞移植受者的腺病毒疾病。

Treatment of adenovirus disease in stem cell transplant recipients with cidofovir.

作者信息

Neofytos Dionissios, Ojha Ambrish, Mookerjee Bijoyesh, Wagner John, Filicko Joanne, Ferber Andres, Dessain Scott, Grosso Dolores, Brunner Janet, Flomenberg Neal, Flomenberg Phyllis

机构信息

Division of Infectious Diseases and Environment Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

出版信息

Biol Blood Marrow Transplant. 2007 Jan;13(1):74-81. doi: 10.1016/j.bbmt.2006.08.040.

Abstract

Invasive adenovirus (AdV) disease is fatal in >50% of allogeneic hematopoietic stem cell transplant (SCT) recipients. Treatment with cidofovir may improve outcomes based on in vitro susceptibility data and case reports. Six consecutive cases of invasive AdV disease treated with cidofovir were reviewed among 84 allogeneic adult SCT recipients (incidence, 7.1%). Cidofovir was administered intravenously at 5 mg/kg per dose (1-7 doses). All patients received intravenous immune globulin. Blood AdV DNA levels (viral loads, VLs) were monitored with a real-time quantitative polymerase chain reaction assay. Published reports of cidofovir treatment of AdV disease in SCT recipients were critically reviewed. The primary manifestations of AdV disease were hepatitis (n = 3), colitis (n = 2), and nephritis (n = 1). All patients had detectable AdV VLs, with peak values from 5 x 10(5) to 2 x 10(8) copies/mL. All patients received CD34+ selected grafts (n = 3) and/or had graft-versus-host disease (n = 4) and had CD4 counts <100 cells/mm3. Only 1 of 5 patients (20%) who received >or=2 doses of cidofovir died with active AdV disease. Four patients exhibited improvement within days of treatment with cidofovir as documented by clinical criteria and declines in AdV VLs (without a change in immunosuppression). In contrast, 1 patient treated late after onset of AdV disease died after 1 dose of cidofovir. In our review of 70 published cases treated with >or=2 doses of cidofovir, 13 (19%) died from AdV disease. In conclusion, early treatment of AdV disease with cidofovir inhibits viral replication in vivo and reduces mortality in allogeneic SCT recipients compared with historical data.

摘要

侵袭性腺病毒(AdV)疾病在超过50%的异基因造血干细胞移植(SCT)受者中是致命的。根据体外药敏数据和病例报告,西多福韦治疗可能改善预后。在84例成年异基因SCT受者中回顾了6例连续用西多福韦治疗侵袭性AdV疾病的病例(发病率为7.1%)。西多福韦以每剂量5mg/kg静脉给药(1 - 7剂)。所有患者均接受静脉注射免疫球蛋白。采用实时定量聚合酶链反应检测法监测血液AdV DNA水平(病毒载量,VLs)。对已发表的关于西多福韦治疗SCT受者AdV疾病的报告进行了严格审查。AdV疾病的主要表现为肝炎(n = 3)、结肠炎(n = 2)和肾炎(n = 1)。所有患者的AdV VLs均可检测到,峰值为5×10⁵至2×10⁸拷贝/毫升。所有患者均接受了CD34⁺选择的移植物(n = 3)和/或患有移植物抗宿主病(n = 4),且CD4计数<100细胞/mm³。在接受≥2剂西多福韦治疗的5例患者中,仅1例(20%)死于活动性AdV疾病。4例患者在接受西多福韦治疗数天内病情改善,临床标准和AdV VLs下降证明了这一点(免疫抑制无变化)。相比之下,1例在AdV疾病发病后期接受治疗的患者在1剂西多福韦治疗后死亡。在我们对70例接受≥2剂西多福韦治疗的已发表病例的回顾中,13例(19%)死于AdV疾病。总之,与历史数据相比,用西多福韦早期治疗AdV疾病可在体内抑制病毒复制并降低异基因SCT受者的死亡率。

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