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儿童心脏移植受者的移植后淋巴组织增生性疾病。

Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients.

机构信息

Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

出版信息

J Heart Lung Transplant. 2010 Jun;29(6):648-57. doi: 10.1016/j.healun.2010.01.013. Epub 2010 Mar 20.

Abstract

BACKGROUND

Post-transplantation lymphoproliferative disorder (PTLD) is a major cause of morbidity and mortality after pediatric heart transplantation.

METHODS

Heart transplant recipients at The Hospital for Sick Children, Toronto, from 1990 to May 2008, were reviewed. Competing risk hazard analysis was used to model the natural history of the disease. Patients were matched for gender and duration of follow-up to identify potential covariates associated with increased risk of PTLD.

RESULTS

A total of 173 heart transplant recipients (42% <1 year old) were reviewed. Twenty-three developed PTLD at a median of 4 years post-transplantation. After transplantation, PTLD affected 9%, 15% and 28% at 3, 5 and 10 years, respectively. Freedom from death or PTLD recurrence was 72%, 58% and 50% at 1, 3 and 5 years, respectively, after PTLD diagnosis. Higher maximum Epstein-Barr viral (EBV) load (hazard ratio [HR]: 2.6, p = 0.004) and longer duration of induction therapy (HR: 1.7, p = 0.02) were associated with increased risks of PTLD. Higher cumulative cyclosporine doses over the first year post-transplantation were associated with increased risks of PTLD (HR: 1.2 per 1 mg/kg/day equivalent, p = 0.03), but higher tacrolimus doses were not (p = 0.38). Patients on cyclosporine at 6 months post-transplantation were at higher risk of PTLD than those on tacrolimus (HR: 5.2, p = 0.003). The use of anti-viral prophylaxis in patients with high EBV load may provide some protection (HR: 7.6 vs 15.4 with no anti-viral, p = 0.02).

CONCLUSIONS

PTLD is a major concern in pediatric heart transplant recipients and is associated with high morbidity/mortality. Exposure to EBV and higher intensity of immunosuppression seems to be associated with increased risk.

摘要

背景

移植后淋巴组织增生性疾病(PTLD)是儿童心脏移植后发病率和死亡率的主要原因。

方法

回顾了多伦多 SickKids 医院 1990 年至 2008 年 5 月期间的心脏移植受者。使用竞争风险风险分析来对疾病的自然史进行建模。对性别和随访时间进行匹配,以确定与 PTLD 风险增加相关的潜在协变量。

结果

共回顾了 173 例心脏移植受者(42%<1 岁)。23 例在移植后中位时间 4 年后发生 PTLD。移植后,PTLD 在 3、5 和 10 年后的发生率分别为 9%、15%和 28%。PTLD 诊断后 1、3 和 5 年的无死亡或 PTLD 复发的生存率分别为 72%、58%和 50%。更高的 EBV 载量(HR:2.6,p=0.004)和更长的诱导治疗时间(HR:1.7,p=0.02)与 PTLD 的风险增加相关。移植后第一年累积环孢素剂量较高与 PTLD 风险增加相关(HR:每 1mg/kg/天等效剂量增加 1.2,p=0.03),但他克莫司剂量较高则无此关联(p=0.38)。移植后 6 个月时使用环孢素的患者比使用他克莫司的患者发生 PTLD 的风险更高(HR:5.2,p=0.003)。在 EBV 载量高的患者中使用抗病毒预防可能提供一些保护(HR:7.6 比无抗病毒治疗时的 15.4,p=0.02)。

结论

PTLD 是儿童心脏移植受者的一个主要问题,与高发病率/死亡率相关。接触 EBV 和更强的免疫抑制似乎与风险增加有关。

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