Cesaro S, Zhou X, Manzardo C, Buonfrate D, Cusinato R, Tridello G, Mengoli C, Palù G, Messina C
Pediatric Hematology-Oncology Clinic, Department of Pediatrics, University of Padova, 35128 Padova, Italy.
J Clin Virol. 2005 Oct;34(2):129-32. doi: 10.1016/j.jcv.2005.02.009. Epub 2005 Apr 14.
Cidofovir (CDV) is a nucleotide analogue with broad antiviral activity. This drug has a very favorable pharmacokinetic profile that enables intermittent dosing, but the potential for nephrotoxicity has hitherto restricted its use in stem cell transplant recipients. Data on pediatric patients are limited.
To report the efficacy and toxicity of CDV in a group of pediatric patients with cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation.
Prospective evaluation of safety and efficacy of CDV used pre-emptively for CMV reactivation in 10 out of 30 children who underwent allogeneic hematopoietic stem cell transplantation from January 2000 to December 2001. In all the patients but one, CDV was used as second-line therapy (after foscarnet or ganciclovir) of CMV reactivation.
Overall, 12 courses of CDV were administered with a median 5 doses per course, range 1-6 (two patients were treated twice). Considering the first CDV treatment episode, 8 out of 10 patients had positive CMV antigenemia assay when they started CDV. Five of eight antigenemic patients responded completely while three were switched to foscarnet or ganciclovir, respectively, due to increasing (one) or persistent CMV antigenemia (two). Overall, the therapy with CDV was well tolerated, but it was withdrawn in one patient due to a two-fold increase in the baseline creatinine level. This patient concurrently had a high tacrolimus blood level.
Safety is the major concern regarding the use of CDV but the adoption of probenicid, intravenous hydration and anti-emetic therapy improved its tolerability profile. Our data suggest that CDV has an acceptable toxicity and would deserve further controlled studies in the setting of pre-emptive therapy for CMV.
西多福韦（CDV）是一种具有广泛抗病毒活性的核苷酸类似物。该药物具有非常良好的药代动力学特征，能够进行间歇性给药，但迄今为止，其潜在的肾毒性限制了它在干细胞移植受者中的应用。关于儿科患者的数据有限。
报告CDV在一组异基因干细胞移植后发生巨细胞病毒（CMV）激活的儿科患者中的疗效和毒性。
对2000年1月至2001年12月接受异基因造血干细胞移植的30名儿童中的10名进行前瞻性评估，这些儿童在CMV激活时预先使用CDV的安全性和有效性。除一名患者外，所有患者均将CDV用作CMV激活的二线治疗（在膦甲酸钠或更昔洛韦之后）。
总体而言，共给予12个疗程的CDV，每个疗程的中位剂量为5剂，范围为1 - 6剂（两名患者接受了两次治疗）。考虑首次CDV治疗阶段，10名患者中有8名在开始使用CDV时CMV抗原血症检测呈阳性。8名抗原血症患者中有5名完全缓解，3名分别因CMV抗原血症增加（1名）或持续存在（2名）而改用膦甲酸钠或更昔洛韦。总体而言，CDV治疗耐受性良好，但有一名患者因基线肌酐水平升高两倍而停药。该患者同时他克莫司血药浓度较高。
使用CDV的主要关注点是安全性，但采用丙磺舒、静脉补液和止吐治疗可改善其耐受性。我们的数据表明，CDV具有可接受的毒性，值得在CMV抢先治疗中进行进一步的对照研究。
