Opelz Gerhard, Naujokat Cord, Daniel Volker, Terness Peter, Döhler Bernd
Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
Transplantation. 2006 May 15;81(9):1227-33. doi: 10.1097/01.tp.0000219817.18049.36.
It is widely assumed that the graft-enhancing properties of antilymphocyte induction agents and their lymphoma-inducing potential are intimately related.
The Collaborative Transplant Study (CTS) database was used to evaluate graft survival and non-Hodgkin lymphoma at 3 years according to type of induction in 112,122 patients receiving a deceased-donor renal transplant during 1985 to 2004.
The relative risk of 3-year graft loss versus no induction was 1.07 (95% confidence interval [CI], 1.01-1.13; P=0.016) with murine anti-CD3 monoclonal antibody (OKT3), 1.03 (95% CI, 0.95-1.11; NS) with antithymocyte globulin (ATG)-Fresenius, 1.18 (95% CI, 1.02-1.35; P=0.021) with ATGAM, 0.74 (95% CI, 0.68-0.81; P<0.001) with Thymoglobulin, and 0.78 (95% CI, 0.72-0.84; P<0.001) with interleukin (IL)-2RA induction. The standardized incidence ratio of lymphoma compared with a similar nontransplant population was 21.5 (95% CI, 15.7-28.8; P<0.001) with OKT3, 4.9 (95% CI, 1.6-11.5; P=0.008) with ATG-Fresenius, 29.0 (95% CI, 12.5-57.1; P<0.001) with ATGAM, 21.6 (95% CI, 14.3-31.2; P<0.001) with Thymoglobulin, 7.8 (95% CI, 4.4-12.9; P<0.001) with IL-2RAs, and 9.4 (95% CI, 8.3-10.6 P<0.001) with no induction.
Those agents that offered the highest rates of graft survival were not necessarily associated with the highest risk of lymphoma. Graft survival was significantly improved with Thymoglobulin and IL-2RA induction, whereas lymphoma rates were highest with ATGAM, OKT3, and Thymoglobulin. IL-2RA agents seem to offer the best risk-to-benefit ratio for this patient population overall in terms of graft survival and lymphoma.
人们普遍认为抗淋巴细胞诱导剂的移植物增强特性与其致淋巴瘤潜力密切相关。
协作移植研究（CTS）数据库用于评估1985年至2004年期间接受尸体供肾移植的112,122例患者根据诱导类型在3年时的移植物存活情况和非霍奇金淋巴瘤情况。
与未进行诱导相比，使用鼠抗CD3单克隆抗体（OKT3）时3年移植物丢失的相对风险为1.07（95%置信区间[CI]，1.01 - 1.13；P = 0.016），使用抗胸腺细胞球蛋白（ATG）-费森尤斯时为1.03（95% CI，0.95 - 1.11；无统计学意义），使用ATGAM时为1.18（95% CI，1.02 - 1.35；P = 0.021），使用胸腺球蛋白时为0.74（95% CI，0.68 - 0.81；P < 0.001），使用白细胞介素（IL）-2受体拮抗剂诱导时为0.78（95% CI，0.72 - 0.84；P < 0.001）。与类似的非移植人群相比，使用OKT3时淋巴瘤的标准化发病比为21.5（95% CI，15.7 - 28.8；P < 0.001），使用ATG-费森尤斯时为4.9（95% CI，1.6 - 11.5；P = 0.008），使用ATGAM时为29.0（95% CI，12.5 - 57.1；P < 0.001），使用胸腺球蛋白时为21.6（95% CI，14.3 - 31.2；P < 0.001），使用IL-2受体拮抗剂时为7.8（95% CI，4.4 - 12.9；P < 0.001），未进行诱导时为9.4（95% CI，8.3 - 10.6；P < 0.001）。
那些移植物存活率最高的药物不一定与淋巴瘤的最高风险相关。使用胸腺球蛋白和IL-2受体拮抗剂诱导时移植物存活率显著提高，而使用ATGAM、OKT3和胸腺球蛋白时淋巴瘤发生率最高。就移植物存活和淋巴瘤而言，IL-2受体拮抗剂总体上似乎为该患者群体提供了最佳的风险效益比。
