26例原发性免疫缺陷病患儿造血干细胞移植后巨细胞病毒感染分析

Clinical study on cytomegalovirus infection after hematopoietic stem cell transplantation in 26 patients with primary immunodeficiency diseases

目的 探讨原发性免疫缺陷病（PID）患儿造血干细胞移植（HSCT）后发生CMV感染的危险因素及其防治措施.方法 回顾性分析行HSCT的26例PID患儿病例资料,其中湿疹、血小板减少伴免疫缺陷综合征20例,重症联合免疫缺陷1例,X连锁-慢性肉芽肿病2例,X连锁-高IgM综合征3例.移植前、后采用ELISA、定量PCR每周定期监测CMV感染状态;应用更昔洛韦或膦甲酸治疗.结果 26例患儿均为男性,中位移植年龄27（7～77）个月.中位随访24（5～66）个月,5年总体生存率为（75.0±9.0）％.26例患儿中11例（42.3％）移植后发生CMV活动性感染,经治疗后9例好转,2例发展为CMV相关性间质性肺炎.单因素分析结果显示移植后CMV活动性及非活动性感染组患儿在移植前的CMV感染发生率差异有统计学意义（62.5％对10.0％,P=0.010）;而两组间移植物种类、供受者关系及HLA相合程度、急性移植物抗宿主病程度差异均无统计学意义（P值均＞0.05）.结论 CMV感染为PID患儿HSCT后的主要并发症之一,定期监测、早期诊断和及时治疗对改善移植患者预后有重要意义.

Objective To explore the risk factors, and control measures of cytomegalovirus （CMV） infection after hematopoietic stem cell transplantion （HSCT） in children with primary immunodefi ciency diseases （PID）. Methods We retrospectively analyzed results of 26 patients with PID-Wiskott- Aldrich syndrome （WAS, n=20） , severe combined immunodeficiency （SCID, n=1）, X-linked chronic granulomatous disease （XCGD, n=2） and X- linked hyper-immunoglobulin M （IgM） syndrome （XHIM, n=3） -who underwent HSCT from June 2007 to December 2012 in our center. Serologic studies （ELISA） and weekly CMV infection surveillance （quantitative PCR, qPCR） were routinely performed before and after HSCT. Ganciclovir or forcamet was used for pre-emptive and curative therapy. Results All 26 patients were male with the median age at HSCT of 27 months （range 7-77 months）. At a median follow up of 24 months （range 5-66 months）, the 5-year overall survival rate was （75.0-4-9.0）%. CMV infection occurred in 42.3% （11 of 26） of the patients, two of them developed CMV interstitial pneumonia （CMV- IP）. Univariate analysis revealed that the incidence of pre-transplant CMV infection between with and without CMV activation groups after HSCT was significantly different （62.5% vs 10.0%, P=0.010）. Additional variables not associated with CMV infection were stem-cell sources, donor type, HLA disparity and acute GVHD （all P values〉0.05）. Conclusions CMV infection was a major complication of HSCT. Sensitive monitoring, early diagnosis, timely treatment may improve the survival rate for these PID undergoing HSCT.