Moretti S, Zikos P, Van Lint M T, Tedone E, Occhini D, Gualandi F, Lamparelli T, Mordini N, Berisso G, Bregante S, Bruno B, Bacigalupo A
Divisione Ematologia II, Ospedale San Martino, Genova, Italy.
Bone Marrow Transplant. 1998 Jul;22(2):175-80. doi: 10.1038/sj.bmt.1701302.
This trial was designed to compare foscarnet with ganciclovir as pre-emptive therapy for CMV infection in patients undergoing allogeneic hemopoietic stem cell transplant (HSCT). Thirty-nine patients were randomized to receive foscarnet 90 mg/kg every 12 h (n = 20) or ganciclovir 5 mg/kg every 12 h (n = 19) for 15 days at the time of development of CMVAg-emia. Primary-end points of the study were (1) outcome of CMVAg-emia; (2) progression to CMV disease; and (3) side-effects of treatment. The secondary end-point was transplant-related mortality (TRM). The two groups were comparable for diagnosis, status of disease, donor type, acute graft-versus-host (aGVHD) prophylaxis, interval between HSCT and CMVAg-emia and number of CMVAg positive cells; the donor and recipient age were borderline older in the foscarnet group. Increments of serum creatinine in the foscarnet group, and cytopenia in the ganciclovir group were controlled by reducing the administered dose: in the first 15 days of therapy 9/20 foscarnet and 10/19 ganciclovir patients had a dose reduction greater than 20% (P = 0.43). Clearance of CMVAg-emia was faster in the foscarnet group although with borderline statistical significance. Failures of treatment occurred in 3/20 patients in foscarnet group vs 8/19 patients in ganciclovir group (P= 0.06): causes of failure were the need for combination therapy to control antigenemia (1/20 vs 5/19), and reactivation during treatment for 2 vs 3 patients, respectively. CMV disease was diagnosed in 1 vs 2 patients (P = 0.5) who subsequently died. The actuarial 1-year TRM was 25 vs 12%, respectively (P = 0.3). This study suggests that foscarnet and ganciclovir are both effective for pre-emptive therapy of CMVAg-emia, although the number of failures would seem to be slightly higher in the ganciclovir patients. Side-effects are seen in both groups and can be managed with appropriate dose reduction.
本试验旨在比较膦甲酸钠与更昔洛韦作为异基因造血干细胞移植（HSCT）患者巨细胞病毒（CMV）感染抢先治疗的效果。39例患者在出现CMV抗原血症时被随机分为两组，一组每12小时接受90mg/kg膦甲酸钠治疗（n = 20），另一组每12小时接受5mg/kg更昔洛韦治疗（n = 19），疗程15天。该研究的主要终点为：（1）CMV抗原血症的转归；（2）进展为CMV疾病；（3）治疗的副作用。次要终点为移植相关死亡率（TRM）。两组在诊断、疾病状态、供体类型、急性移植物抗宿主病（aGVHD）预防、HSCT与CMV抗原血症之间的间隔时间以及CMV抗原阳性细胞数量方面具有可比性；膦甲酸钠组供体和受者年龄略大。膦甲酸钠组血清肌酐升高以及更昔洛韦组血细胞减少通过减少给药剂量得到控制：在治疗的前15天，20例膦甲酸钠治疗患者中有9例、19例更昔洛韦治疗患者中有10例剂量减少超过20%（P = 0.43）。膦甲酸钠组CMV抗原血症清除更快，尽管具有临界统计学意义。膦甲酸钠组20例患者中有3例治疗失败，更昔洛韦组19例患者中有8例治疗失败（P = 0.06）：失败原因分别是需要联合治疗以控制抗原血症（20例中的1例 vs 19例中的5例）以及分别有2例和3例患者在治疗期间复发。1例和2例患者被诊断为CMV疾病（P = 0.5），随后死亡。1年精算TRM分别为25%和12%（P = 0.3）。本研究表明，膦甲酸钠和更昔洛韦对CMV抗原血症的抢先治疗均有效，尽管更昔洛韦治疗患者的失败例数似乎略多。两组均出现副作用，可通过适当减少剂量进行处理。
