Locatelli F, Percivalle E, Comoli P, Maccario R, Zecca M, Giorgiani G, De Stefano P, Gerna G
Department of Paediatrics, University of Pavia, Italy.
Br J Haematol. 1994 Sep;88(1):64-71. doi: 10.1111/j.1365-2141.1994.tb04978.x.
In a prospective study, we evaluated the role of early treatment with ganciclovir of human cytomegalovirus (HCMV) pp65-antigenaemia, as well as the risk factors related to the infection in 48 paediatric patients given an allogeneic bone marrow transplantation (BMT). HCMV infection occurred in 24 children, the overall actuarial risk of infection at 120 d being 51%. Development of acute graft-versus-host disease (GVHD), steroid therapy and serological status of both recipient and donor were the most powerful predictors of HCMV infection, none of the six seronegative patient/donor pairs developing HCMV infection. Considering only the seropositive recipients and patients given a seropositive marrow (42 cases), the actuarial risk of developing HCMV antigenaemia in patients with acute GVHD was 76% v 27% in those with or without GVHD (P < 0.005) and 79% v 15% respectively in patients who did or did not receive steroid therapy (P < 0.001). HCMV disease developed in 5/24 children with pp65-antigenaemia, which was detected before diagnosis in all cases but one. All patients with pp65-positive cells were treated with ganciclovir at a dose of 5 mg/kg twice daily for 14 d. In patients without acute GVHD no maintenance therapy was administered, whereas children with active acute GVHD were given additional therapy with ganciclovir at a dose of 5 mg/kg/d for 14 d. Ganciclovir produced complete clearing of viraemia and antigenaemia, with some patients presenting recurrences of antigenaemia, which were treated according to the above-mentioned schedule. Likewise, HCMV disease completely resolved after treatment with ganciclovir and no patients died from HCMV-related interstitial pneumonia. Our results suggest that an early short-term therapy with ganciclovir after demonstration of antigenaemia can be effective in reducing or abolishing HCMV-related mortality. This approach eliminates the use of ganciclovir in patients not presenting HCMV reactivation and therefore not benefiting from therapy. The administration of ganciclovir limited to the period needed to obtain antigenaemia clearance could also have the advantage of reducing myelotoxicity.
在一项前瞻性研究中,我们评估了更昔洛韦早期治疗对人巨细胞病毒(HCMV)pp65抗原血症的作用,以及48例接受异基因骨髓移植(BMT)的儿科患者感染相关的危险因素。24名儿童发生了HCMV感染,120天时感染的总体精算风险为51%。急性移植物抗宿主病(GVHD)的发生、类固醇治疗以及受者和供者的血清学状态是HCMV感染最有力的预测因素,6对血清学阴性的患者/供者均未发生HCMV感染。仅考虑血清学阳性的受者和接受血清学阳性骨髓的患者(42例),急性GVHD患者发生HCMV抗原血症的精算风险为76%,而有或无GVHD的患者为27%(P<0.005),接受或未接受类固醇治疗的患者分别为79%和15%(P<0.001)。24例有pp65抗原血症的儿童中有5例发生了HCMV疾病,除1例病例外,所有病例在诊断前均检测到pp65抗原血症。所有pp65阳性细胞的患者均接受更昔洛韦治疗,剂量为5mg/kg,每日2次,共14天。对于无急性GVHD的患者,未给予维持治疗,而患有活动性急性GVHD的儿童则额外接受更昔洛韦治疗,剂量为5mg/kg/d,共14天。更昔洛韦使病毒血症和抗原血症完全清除,部分患者出现抗原血症复发,根据上述方案进行治疗。同样,更昔洛韦治疗后HCMV疾病完全缓解,无患者死于HCMV相关的间质性肺炎。我们的结果表明,在证实抗原血症后早期短期使用更昔洛韦治疗可有效降低或消除HCMV相关的死亡率。这种方法避免了在未出现HCMV再激活、因此无法从治疗中获益的患者中使用更昔洛韦。仅在获得抗原血症清除所需的时间段内给予更昔洛韦,还可能具有降低骨髓毒性的优势。