缬更昔洛韦诱导肝移植受者白细胞减少：霉酚酸酯联合使用的影响

Valganciclovir-induced leukopenia in liver transplant recipients: influence of concomitant use of mycophenolate mofetil.

作者信息

Molina Perez E, Fernández Castroagudín J, Seijo Ríos S, Mera Calviño J, Tomé Martínez de Rituerto S, Otero Antón E, Bustamante Montalvo M, Varo Perez E

机构信息

Abdominal Transplantation Unit, Universitary Hospital Complex of Santiago de Compostela, Spain. esther.molina.perez@sergas

出版信息

Transplant Proc. 2009 Apr;41(3):1047-9. doi: 10.1016/j.transproceed.2009.02.033.

DOI:10.1016/j.transproceed.2009.02.033

PMID:19376423

Abstract

INTRODUCTION

An increased incidence and magnitude of leukopenia during concomitant treatment with valganciclovir (VGC) and mycophenolate mofetil (MMF) has been reported.

OBJECTIVE

To evalute the incidence and severity of leukopenia and neutropenia among liver recipients treated with VGC and related factors.

PATIENTS AND METHODS

Retrospective analysis of clinical and analytical data related to leukopenia (<3000 leukocytes/mm(3)) and neutropenia (<900 neutrophils/mm(3)) in liver transplant patients who were treated with VGC from 2003 to 2007. We examined the influence of concomitant administration of MMF and development of subsequent infections.

RESULTS

Among 209 liver transplants, 40 treatments with VGC were prescribed in 37 patients (17.7%), 12 of which (30%) were associated with MMF. The patients has an average age of 49.7 +/- 12.7, body mass index (BMI) of 27.28 +/- 5.17, and Model for End-stage Liver Disease Score (MELD) 12.45 +/- 7.5. The daily average dose of VGC was 1440 +/- 446.5 mg and MMF, 1454.5 +/- 350.3 mg. We observed a decrease of 30% in initial leukocyte count (5353.7 +/- 2706.6) and 40% in neutrophil count (3600 +/- 2182.1). With no relationship to total dose or BMI-adjusted dose of VGC nor concomitant administration of MMF. The initial leukocyte count was significantly lower (4411 +/- 1930 vs 6206 +/- 3053; P = .03) and underwent a main drop (2344.7 +/- 1974.3 vs 898.1 +/- 2435.6; P = .04) when leukopenia developed. In the induced neutropenia group, previous leukocyte count (3797.1 +/- 1223.9 vs 5683.9 +/- 2829.3; P = .01), MELD (18.7 +/- 8.8 vs 11.1 +/- 6.6; P = .01), and the creatinine pretreatment (1.44 +/- 0.4 vs 1.09 +/- 0.3; P = .01) were significantly different. Subsequent infections induced by the leukopenia were not observed.

CONCLUSIONS

In our series, the concomitant use of VGC and MMF was not associated with a greater incidence of leukopenia and/or neutropenia than VGC administration alone. Previous leukocyte count was associated with them. MELD and renal dysfunction are factors related to severe neutropenia. Leukopenia was not associated with a greater incidence of infections.

摘要

引言

已有报道称，缬更昔洛韦（VGC）与霉酚酸酯（MMF）联合治疗期间白细胞减少症的发生率和严重程度有所增加。

目的

评估接受VGC治疗的肝移植受者中白细胞减少症和中性粒细胞减少症的发生率及严重程度，以及相关因素。

患者与方法

对2003年至2007年接受VGC治疗的肝移植患者中与白细胞减少症（白细胞计数<3000/立方毫米）和中性粒细胞减少症（中性粒细胞计数<900/立方毫米）相关的临床和分析数据进行回顾性分析。我们研究了MMF联合使用的影响以及后续感染的发生情况。

结果

在209例肝移植中，37例患者（17.7%）接受了40次VGC治疗，其中12次（30%）与MMF联合使用。患者的平均年龄为49.7±12.7岁，体重指数（BMI）为27.28±5.17，终末期肝病模型评分（MELD）为12.45±7.5。VGC的日均剂量为1440±446.5毫克，MMF为1454.5±350.3毫克。我们观察到初始白细胞计数下降了30%（5353.7±2706.6），中性粒细胞计数下降了40%（3600±2182.1）。这与VGC的总剂量或BMI调整剂量以及MMF的联合使用均无关。白细胞减少症发生时，初始白细胞计数显著较低（4411±1930对6206±3053；P = 0.03）且出现主要下降（2344.7±1974.3对898.1±2435.6；P = 0.04）。在诱导性中性粒细胞减少症组中，既往白细胞计数（3797.1±1223.9对5683.9±2829.3；P = 0.01）､MELD（18.7±8.8对11.1±6.6；P = 0.01）以及肌酐预处理值（1.44±0.4对1.09±0.3；P = 0.01）存在显著差异。未观察到由白细胞减少症引发的后续感染。