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移植前因治疗原发性肾小球疾病而使用环磷酰胺暴露的肾移植受者中的恶性肿瘤。

Malignancy in Renal Transplant Recipients Exposed to Cyclophosphamide Prior to Transplantation for the Treatment of Native Glomerular Disease.

机构信息

Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.

Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.

出版信息

Pharmacotherapy. 2018 Jan;38(1):51-57. doi: 10.1002/phar.2059. Epub 2017 Dec 18.

Abstract

STUDY OBJECTIVE

To evaluate the risk of posttransplantation malignancy in renal transplant recipients exposed to pretransplantation cyclophosphamide for the treatment of glomerular nephropathy (GN).

DESIGN

Retrospective cohort study.

SETTING

Tertiary academic medical center.

PATIENTS

Six hundred adult renal transplant recipients were transplanted between 1993 and 2014; 54 patients were exposed to pretransplantation cyclophosphamide for treatment of GN (GN-CYC group), and 546 patients with polycystic kidney disease were not exposed to pretransplantation cyclophosphamide (PKD group).

MEASUREMENT AND MAIN RESULTS

Data were collected retrospectively from electronic medical records. The primary outcome was occurrence of posttransplantation malignancy. During a median follow-up of 5.5 years, 130 patients developed malignancy (incidence rate 3.5 events per 100 person-yrs). Exposure to cyclophosphamide before transplantation was significantly associated with malignancy after transplantation (adjusted hazard ratio [aHR] 2.20, 95% confidence interval [CI] 1.16-4.22, p=0.02), specifically skin cancer (aHR 2.24, 95% CI 1.09-4.60, p=0.03). Malignancy risk in the GN-CYC group was higher in the setting of lymphocyte-depleting induction (alemtuzumab; aHR 4.53, 95% CI 0.99-20.72, p=0.05) compared with basiliximab induction. Incidences of death-censored graft loss and mortality were similar between the GN-CYC and PKD groups.

CONCLUSION

In our observational study, renal transplant recipients exposed to pretransplantation cyclophosphamide appeared to have a higher risk of developing a malignancy compared with unexposed renal transplant recipients. Further investigation into the impact of pretransplantation immunosuppression on malignancy, particularly the compounded effect with lymphocyte-depleting induction, is warranted.

摘要

研究目的

评估接受移植前环磷酰胺治疗肾小球肾炎(GN)的肾移植受者发生移植后恶性肿瘤的风险。

设计

回顾性队列研究。

地点

三级学术医疗中心。

患者

1993 年至 2014 年间共进行了 600 例成人肾移植;54 例患者接受移植前环磷酰胺治疗 GN(GN-CYC 组),546 例多囊肾病患者未接受移植前环磷酰胺治疗(PKD 组)。

测量和主要结果

数据从电子病历中回顾性收集。主要结局是发生移植后恶性肿瘤。中位随访 5.5 年后,130 例患者发生恶性肿瘤(发病率为每 100 人年 3.5 例)。移植前使用环磷酰胺与移植后恶性肿瘤显著相关(校正后的危险比[aHR]为 2.20,95%置信区间[CI]为 1.16-4.22,p=0.02),尤其是皮肤癌(aHR 为 2.24,95%CI 为 1.09-4.60,p=0.03)。与 basiliximab 诱导相比,在接受淋巴细胞耗竭诱导(alemtuzumab)的情况下,GN-CYC 组的恶性肿瘤风险更高(aHR 为 4.53,95%CI 为 0.99-20.72,p=0.05)。GN-CYC 组和 PKD 组的死亡相关移植物丢失和死亡率相似。

结论

在我们的观察性研究中,与未暴露于移植前环磷酰胺的肾移植受者相比,接受移植前环磷酰胺治疗的肾移植受者发生恶性肿瘤的风险似乎更高。需要进一步研究移植前免疫抑制对恶性肿瘤的影响,特别是与淋巴细胞耗竭诱导的复合效应。

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