EARLY TREATMENT WITH GANCICLOVIR TO PREVENT CYTOMEGALOVIRUS DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION
EARLY TREATMENT WITH GANCICLOVIR TO PREVENT CYTOMEGALOVIRUS DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION
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DOI：
10.1056/nejm199112053252303
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发表时间：
1991-12-05
影响因子：
158.5
通讯作者：
MEYERS, JD
中科院分区：
文献类型：
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作者：
GOODRICH, JM;MORI, M;MEYERS, JD
背景巨细胞病毒（CMV）感染是异基因骨髓移植后发病和死亡的主要原因。我们进行了一项更昔洛韦早期治疗骨髓移植受者CMV感染的对照试验，这些受者的CMV监测培养结果为阳性。通过咽拭子、血液、尿液或支气管肺泡灌洗液培养筛选CMV抗体血清阳性或接受血清阳性骨髓的骨髓移植受者的CMV排泄。在这项双盲试验中，72名骨髓移植并排出病毒的患者被随机分配接受安慰剂或更昔洛韦（5 mg/kg体重，每天两次，持续一周，随后每天5 mg/kg体重），在移植后的前100天内。随访患者活检证实的CMV疾病、更昔洛韦相关毒性和生存率。在分配到研究药物和移植后100天之间，CMV疾病在分配到接受更昔洛韦的37名患者中仅发生1例（3%），但在分配到接受安慰剂的35名患者中有15例（43%，P < 0.00001）。接受更昔洛韦的患者病毒排泄迅速受到抑制; 85%的患者在治疗一周后培养阴性，而安慰剂组为44%（P = 0.001）。主要的毒性反应是中性粒细胞减少; 11名更昔洛韦接受者的中性粒细胞绝对计数低于0.75 × 10（9）/L，而安慰剂接受者为3名（P = 0.052）。11例更昔洛韦接受者和1例安慰剂接受者因中性粒细胞减少而停止治疗（P = 0.003）。治疗停止后，所有患者的中性粒细胞计数均恢复正常。移植后100天和180天更昔洛韦组的总生存率均显著高于安慰剂组（P分别为0.041和0.027）。早期更昔洛韦治疗监测培养阳性的患者可降低巨细胞病毒病的发生率，提高异基因骨髓移植后的生存率。
Background. Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir for the early treatment of CMV infection in asymptomatic recipients of bone marrow transplants whose surveillance cultures for CMV became positive.Methods. Bone marrow-allograft recipients who were seropositive for CMV antibodies or who received seropositive marrow were screened for CMV excretion by culture of throat swabs, blood, urine, or bronchoalveolar-lavage fluid. In this double-blind trial, 72 patients who had marrow engraftment and were excreting virus were randomly assigned to receive either placebo or ganciclovir (5 mg per kilogram of body weight twice a day for one week, followed by 5 mg per kilogram per day) for the first 100 days after transplantation. Patients were followed for the development of biopsy-confirmed CMV disease, ganciclovir-related toxicity, and survival.Results. Between assignment to the study drug and day 100 after transplantation, CMV disease developed in only 1 of the 37 patients assigned to receive ganciclovir (3 percent), but in 15 of the 35 patients assigned to receive placebo (43 percent, P < 0.00001). The ganciclovir recipients had rapid suppression of virus excretion; 85 percent had negative cultures after one week of treatment, as compared with 44 percent of the placebo group (P = 0.001). The principal toxic reaction was neutropenia; 11 ganciclovir recipients had an absolute neutrophil count below 0.75 x 10(9) per liter, as compared with 3 placebo recipients (P = 0.052). Treatment was discontinued in 11 ganciclovir recipients and 1 placebo recipient because of neutropenia (P = 0.003). After treatment was stopped, the neutrophil count recovered in all patients. Overall survival was significantly greater in the ganciclovir group than in the placebo group both 100 days and 180 days after transplantation (P = 0.041 and 0.027, respectively).Conclusions. Early treatment with ganciclovir in patients with positive surveillance cultures reduces the incidence of CMV disease and improves survival after allogeneic bone marrow transplantation.