Braconnier Philippe, Del Marmol Véronique, Broeders Nilufer, Kianda Mireille, Massart Annick, Lemy Anne, Ghisdal Lidia, Le Moine Alain, Madhoun Philippe, Racapé Judith, Abramowicz Daniel, Wissing Karl Martin
Renal Transplantation Clinic, Department of Nephrology, ULB Hopital Erasme, Brussels, Belgium.
Nephrol Dial Transplant. 2012 Jun;27(6):2547-53. doi: 10.1093/ndt/gfr627. Epub 2011 Nov 28.
Several studies suggest that the introduction of tacrolimus (TRL), mycophenolic acid (MPA) and interleukin 2 receptor antibodies (IL2Ra) as single drugs more than a decade ago has not increased the risk of malignancy after renal transplantation. However, only limited data are available on their carcinogenic effects when used in combination as a potent immunosuppressive regimen.
A retrospective single-centre cohort study on 929 adult renal transplant recipients. Investigation of the effect of two consecutive immunosuppressive regimens [1993-98, N = 405, anti-lymphocyte antibodies, cyclosporine and azathioprine (AZA); 1999-2007, N = 524, predominantly IL2Ra, TRL and MPA] on the incidence rate of skin cancer, solid tumours and post-transplant lymphoproliferative disease (PTLD).
In total, 365 malignancies developed among 113 patients. As compared to the previous cyclosporine and AZA-based immunosuppression, the introduction of the new immunosuppressive regimen did not increase the incidence rate of skin cancer [rate ratio 0.84; 95% confidence interval (CI) 0.48-1.46], solid tumours (0.89; 95% CI 0.46-1.67) and PTLD (0.82; 95% CI 0.28-2.21). Patients treated with the more recent regimens less frequently developed multiple skin cancers and invasive squamous cell cancer. Skin cancer after transplantation was strongly associated with the development of solid tumours (odds ratio 5.2; P < 0.0001). The introduction of the new immunosuppressive drugs reduced the incidence of first year acute rejection from 34.8 to 13.2% (P < 0.0001).
Although significantly more efficient in the prevention of acute rejection, the introduction of TRL, MPA and IL2Ra-based immunosuppression after kidney transplantation was not associated with an increased incidence of skin cancer, solid tumours or PTLD.
多项研究表明,十多年前作为单一药物引入的他克莫司(TRL)、霉酚酸(MPA)和白细胞介素2受体抗体(IL2Ra)并未增加肾移植后发生恶性肿瘤的风险。然而,关于它们作为强效免疫抑制方案联合使用时的致癌作用,仅有有限的数据。
对929例成年肾移植受者进行一项回顾性单中心队列研究。调查两种连续免疫抑制方案[1993 - 1998年,N = 405,抗淋巴细胞抗体、环孢素和硫唑嘌呤(AZA);1999 - 2007年,N = 524,主要是IL2Ra、TRL和MPA]对皮肤癌、实体瘤和移植后淋巴细胞增生性疾病(PTLD)发病率的影响。
113例患者共发生365例恶性肿瘤。与先前基于环孢素和AZA的免疫抑制相比,新免疫抑制方案的引入并未增加皮肤癌[率比0.84;95%置信区间(CI)0.48 - 1.46]、实体瘤(0.89;95% CI 0.46 - 1.67)和PTLD(0.82;95% CI 0.28 - 2.21)的发病率。接受较新方案治疗的患者发生多发性皮肤癌和浸润性鳞状细胞癌的频率较低。移植后皮肤癌与实体瘤的发生密切相关(优势比5.2;P < 0.0001)。新免疫抑制药物的引入使第一年急性排斥反应的发生率从34.8%降至13.2%(P < 0.0001)。
尽管在预防急性排斥反应方面效率显著提高,但肾移植后引入基于TRL、MPA和IL2Ra的免疫抑制与皮肤癌、实体瘤或PTLD的发病率增加无关。