Doesch A O, Müller S, Konstandin M, Celik S, Kristen A, Frankenstein L, Ehlermann P, Sack F-U, Katus H A, Dengler T J
Department of Cardiology, University of Heidelberg, Germany.
Transplant Proc. 2010 Nov;42(9):3694-9. doi: 10.1016/j.transproceed.2010.07.107.
The objectives of the present study were to evaluate the incidence of malignancies and to describe the effects of immunosuppression on survival and recurrence of malignancies after heart transplantation (HTX). Data were analyzed in 211 cardiac allograft recipients, in whom HTX was performed between 1989 and 2005. All of these patients survived for more than 2 years after HTX and received induction therapy with antithymocyte globulin (RATG) guided by T-cell monitoring since 1994. An immunosuppressive regimen consisting of cyclosporine A (CsA) combined with azathioprine was followed by CsA and mycophenolate mofetil (MMF) in 2001; mammalian target of rapamycin (mTOR) inhibitors (everolimus/sirolimus) were used since 2003. Mean patient age at HTX was 51.4 ± 10.5 years; mean follow-up time after HTX 9.2 ± 4.7 years. Overall incidence of neoplasias was 30.8%. Individual risk factors associated with a higher risk of malignancy after HTX were higher age at transplantation (P = .003), male gender (P = .005) and ischemic cardiomyopathy before HTX (P = .04). Administration of azathioprine (P < .0001) or a calcineurin inhibitor (CNI) (P = .02) for more than 1 year was associated with development of malignancy, whereas significantly fewer malignancies were noticed in patients receiving an mTOR-inhibitor (P < .0001). Kaplan-Meier analysis demonstrated a strong statistical trend toward an improved survival in patients with a noncutaneous neoplasia switched to a CNI-free protocol (P = .05). This study demonstrated the impact of a variety of individual risk factors and immunosuppressive drugs on development of malignancy after HTX. Markedly fewer patients with noncutaneous malignancies died after switch to a CNI-free regimen, not quite reaching statistical significance by Kaplan-Meier analysis, however.
本研究的目的是评估恶性肿瘤的发生率，并描述免疫抑制对心脏移植（HTX）后恶性肿瘤生存和复发的影响。对211例心脏移植受者的数据进行了分析，这些患者在1989年至2005年间接受了HTX。所有这些患者在HTX后存活超过2年，自1994年起接受以T细胞监测为指导的抗胸腺细胞球蛋白（RATG）诱导治疗。免疫抑制方案最初为环孢素A（CsA）联合硫唑嘌呤，2001年改为CsA和霉酚酸酯（MMF）；自2003年起使用哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂（依维莫司/西罗莫司）。HTX时患者的平均年龄为51.4±10.5岁；HTX后的平均随访时间为9.2±4.7年。肿瘤的总体发生率为30.8%。与HTX后发生恶性肿瘤风险较高相关的个体危险因素包括移植时年龄较大（P = 0.003）、男性（P = 0.005）和HTX前的缺血性心肌病（P = 0.04）。使用硫唑嘌呤（P < 0.0001）或钙调神经磷酸酶抑制剂（CNI）（P = 0.02）超过1年与恶性肿瘤的发生相关，而接受mTOR抑制剂的患者中恶性肿瘤的发生率明显较低（P < 0.0001）。Kaplan-Meier分析显示，转换为无CNI方案的非皮肤肿瘤患者的生存率有显著改善的统计学趋势（P = 0.05）。本研究证明了多种个体危险因素和免疫抑制药物对HTX后恶性肿瘤发生的影响。然而，转换为无CNI方案后，非皮肤恶性肿瘤患者的死亡人数明显减少，通过Kaplan-Meier分析未完全达到统计学意义。
