Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study
Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study
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DOI：
10.1038/sj.bmt.1702450
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发表时间：
2000-07-01
影响因子：
4.8
通讯作者：
Bacigalupo, A
中科院分区：
文献类型：
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作者：
Bregante, S;Bertilson, S;Bacigalupo, A
这是一项在20例高危患者（无关供体、T细胞耗竭和/或晚期疾病）中进行的异基因骨髓移植（BMT）后使用膦甲酸预防CMV的剂量探索研究。在BMT后第+1天开始膦甲酸，并持续至第+100天。我们探索了四种不同的剂量水平，患者以最低剂量水平入组，直至一名患者发生CMV再激活，确定为连续两次阳性CMV抗原血症（CMVAg血症）。第1 - 30天（诱导）和第31 - 100天（维持）之间的4个剂量水平（以mg/kg/天表示）分别为：剂量水平I = 60/30（n = 5）;剂量水平II = 120/60（n = 4）;剂量水平III = 120/90（n = 5）和剂量水平IV = 120/120（n = 6）。所有患者均显示植入：骨髓移植后第16、21、17、15天中性粒细胞≥ 0.5 × 10（9）/l，第19、16、17、17天Pit ≥ 30 × 10（9）/l。在10例患者中观察到CMVAg血症，中位间隔时间为骨髓移植后53天（范围33-89），中位数为10个CMV抗原+细胞膦甲酸钠对CMV Ag血症有剂量效应：剂量水平I、II、III、IV分别为4/5例患者（80%）、2/4例（50%）、3/5例（60%）和1/6例（18%）（P = 0.1）。在剂量水平I、II和剂量水平III、IV下分别有3/9（33%）和0/11例患者观察到CMV疾病（P = 0.07），诊断CMV感染时CMV抗原阳性细胞的中位数不同：I-II剂量水平13例，m-Iv剂量水平2例（P = 0.01），在15例患者中观察到肌酐升高，平均值为1.8 mg%（范围1.5-5.7），这是9例患者（45%）停药的原因。所有9例患者的肾毒性均可逆。2年时的总体精算TRM为31%：剂量水平I-II的患者为47%，剂量水平III-IV的患者为19%。总之，膦甲酸对CMV Ag血症、CMV病和移植相关死亡率具有剂量依赖性预防作用，肾毒性可接受且可逆。
This is a dose-finding study using,foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100, We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6. All patients showed engraftment: PMN greater than or equal to 0.5 x 10(9)/l at a median interval of 16, 21, 17, 15 days after BMT, and Pit greater than or equal to 30 x 10(9)/l on days 19,16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16), There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0.07), The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels m-Iv (P = 0.01), Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. hi conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.