一项关于高剂量多价静脉注射免疫球蛋白（HDIgG）与巨细胞病毒（CMV）高免疫球蛋白在异基因造血干细胞移植（HSCT）中的随机试验。

A randomized trial of high dose polyvalent intravenous immunoglobulin (HDIgG) vs. Cytomegalovirus (CMV) hyperimmune IgG in allogeneic hemopoietic stem cell transplants (HSCT).

作者信息

Zikos P, Van Lint M T, Lamparelli T, Gualandi F, Occhini D, Mordini N, Berisso G, Bregante S, Bacigalupo A

机构信息

Divisione Ematologia II, Ospedale San Martino, Genoa, Italy.

出版信息

Haematologica. 1998 Feb;83(2):132-7.

PMID:9549924

Abstract

BACKGROUND AND OBJECTIVE

The role of high dose intravenous IgG (HDIgG) and of hyperimmune CMV IgG (CMV-IgG) in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT) is still unclear. The aim of this study was to compare prophylactic CMV-IgG with HDIgGin a randomized prospective trial in allogeneic HSCT recipients: primary end point of the study was the occurrence of post-transplant CMV antigenemia (CMVAg-emia). Secondary end-points were severity of acute and chronic graft-versus-host disease (GvHD), infections and transplant related mortality (TRM).

DESIGN AND METHODS

Patients were randomized to receive 100 mg/kg/week of CMV-IgG (group A; n = 64) or 400 mg/kg/week of HDIgG (group B; n = 64) from day -7 to day +100. The two groups were comparable for age, diagnosis, disease status, and acute graft-versus host (aGvHD) prophylaxis.

RESULTS

The actuarial risk at 1 year of CMV antigenemia was lower for CMV-IgG (61% vs. 71%) but not significantly (p = 0.37); CMVAg-emia occurred at the same interval from HSCT (47 vs. 48 days, p = 0.9), with a comparable number of CMVAg positive cells (3 vs. 3 p = 0.9). Eight patients died of interstitial pneumonia (IP) (4 in each group), two in group A of CMV-IP. Acute GvHD was scored as O-I, II and III-IV in 39 vs. 35, 23 vs. 22 and 2 vs. 7 patients respectively for the two groups (p = not significant). The actuarial risk of developing acute GvHD grade II-IV was lower for CMV-IgG (39% vs. 45%) but not significantly (p = 0.43). Chronic GvHD scored as absent in 7 vs. 10 patients, limited in 39 vs. 37 and extensive in 19 vs. 17 patients respectively (p = not significant). Numbered days with intravenous antibiotics, days in hospital, days of fever, number of local and disseminated infections, number of patients with fever of unknown origin were not significantly different. Actuarial 1 year TRM is 18% vs. 19%, respectively (p = 0.9).

INTERPRETATION AND CONCLUSIONS

This study confirms that CMV antigenemia is comparable in recipients of hyperimmune CMV-IgG and of polyvalent HDIgG, although the former had a 32% lower cost. It also shows that the potential immunomodulating effect on acute GvHD and transplant mortality is similar with 100 or 400 mg of IgG/kg/week: this is relevant, in view of the high cost of prophylactic HDIgG.

摘要

背景与目的

大剂量静脉注射免疫球蛋白（HDIgG）和高免疫性巨细胞病毒免疫球蛋白（CMV-IgG）在接受异基因造血干细胞移植（HSCT）患者中的作用仍不明确。本研究旨在通过一项针对异基因HSCT受者的随机前瞻性试验，比较预防性使用CMV-IgG和HDIgG：该研究的主要终点是移植后巨细胞病毒抗原血症（CMVAg血症）的发生情况。次要终点包括急性和慢性移植物抗宿主病（GvHD）的严重程度、感染及移植相关死亡率（TRM）。

设计与方法

从第-7天至第+100天，将患者随机分为两组，分别接受每周100mg/kg的CMV-IgG（A组；n = 64）或每周400mg/kg的HDIgG（B组；n = 64）。两组在年龄、诊断、疾病状态及急性移植物抗宿主病（aGvHD）预防措施方面具有可比性。

结果

CMV-IgG组1年时CMV抗原血症的精算风险较低（61%对71%），但差异无统计学意义（p = 0.37）；CMVAg血症在HSCT后相同时间间隔出现（47天对48天，p = 0.9），CMVAg阳性细胞数量相当（3对3，p = 0.9）。8例患者死于间质性肺炎（IP）（每组4例），A组2例死于CMV-IP。两组急性GvHD分级为O-I、II和III-IV的患者分别为39对35、23对22和2对7例（p = 无显著差异）。CMV-IgG组发生II-IV级急性GvHD的精算风险较低（39%对45%），但差异无统计学意义（p = 0.43）。慢性GvHD评分中，分别有7对10例患者无、39对37例患者有限及19对17例患者广泛受累（p = 无显著差异）。静脉使用抗生素的天数、住院天数、发热天数、局部和播散性感染的数量、不明原因发热患者的数量差异均无统计学意义。1年精算TRM分别为18%对19%（p = 0.9）。