Crespo-Leiro Maria G, Alonso-Pulpón Luis, Arizón José M, Almenar Luis, Delgado Juan F, Palomo Jesús, Manito Nicolás, Rábago Gregorio, Lage Ernesto, Diaz Beatriz, Roig Eulalia, Pascual Domingo, Blasco Teresa, de la Fuente Luis, Campreciós Marta, Vázquez de Prada José A, Muñiz Javier
Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain.
J Heart Lung Transplant. 2007 Nov;26(11):1105-9. doi: 10.1016/j.healun.2007.08.010.
Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma.
This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003.
Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used.
Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.
心脏移植（HT）后发生的淋巴瘤与诱导治疗及疱疹病毒感染有关。目前尚不清楚HT术后立即使用抗病毒药物是否能降低淋巴瘤的发病率。
本研究对1984年至2003年12月间在西班牙接受HT的3393例患者进行了回顾性分析。所检查的变量包括淋巴瘤的发生情况，以及作为可能危险因素的受者性别和年龄、诱导治疗（抗胸腺细胞球蛋白、OKT3和抗白细胞介素-2受体抗体）和抗病毒预防措施（阿昔洛韦或更昔洛韦）。为研究不断演变的治疗策略的影响，将HT分为三个时期：1984年至1995年；1996年至2000年；以及2001年至2003年。
超过60%的HT患者接受了诱导治疗，超过50%的患者接受了抗病毒预防。共有62例淋巴瘤病例（每1000人年3.1例，95%置信区间：2.4至4.0）。单因素分析显示，性别、移植时年龄、HT时期、HT前吸烟情况或HT后前3个月使用的免疫抑制维持药物均无影响。诱导剂抗胸腺细胞球蛋白（ATG）与淋巴瘤风险增加相关，而阿昔洛韦预防则与淋巴瘤风险降低相关。多因素分析（控制年龄组、性别、HT前吸烟情况以及前3个月使用霉酚酸酯和/或他克莫司进行免疫抑制）显示，如果未使用抗病毒预防（无论诱导剂和抗病毒药物如何），诱导会增加淋巴瘤风险，但如果使用抗病毒预防则不会增加风险。
使用ATG或OKT3进行诱导治疗是否会增加淋巴瘤风险，分别取决于是否使用阿昔洛韦或更昔洛韦进行抗病毒预防。
