Orr Christopher, Stratton Jeannette, El-Shahawy Mohamed, Forouhar Elena, Peng Alice, Singh Gagandeep, Omori Keiko, Qi Meirigeng, Kandeel Fouad
Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA.
Kidney & Pancreas Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA. USA.
Cell Transplant. 2025 Jan-Dec;34:9636897241309412. doi: 10.1177/09636897241309412.
Herein, we characterized the percentage of tacrolimus to the combined sirolimus and tacrolimus trough levels (tacrolimus %) observed during islet transplant-associated immune suppression therapy with post-transplant skin cancer. Although trough levels of tacrolimus and sirolimus were not different ( = 0.79, 0.73, respectively), high tacrolimus % resulted in a 1.32-fold increase in skin cancer odds when adjusting for age, sex, body mass index (BMI), and use of mycopheonlate mofetil (MMF; = 0.039). Skin cancer patients were likely to have been older but not differ significantly (mean difference 12 years, = 0.056), but age was significantly associated with a 1.22-fold increase in adjusted skin cancer odds ( = 0.046). BMI was inversely associated with skin cancer, with an adjusted odds ratio (OR) of 0.40 ( = 0.022). High tacrolimus % (>35) resulted in a 4.6-fold increase in skin cancer frequency, whereas sirolimus above 75% of the combined therapy led to a 5.2-fold increase in islet graft dysfunction (IGD) events/year. By calculating the maximum safe exposure (MSE) to tacrolimus % according to patient age and BMI, we found that cumulative months spent above MSE was predictive of skin cancer (1.20-fold increase, = 0.003). Individuals exceeding the MSE for 1 year were 9.2 times more likely to develop skin cancer ( = 0.008). Results suggest that strategies targeting immunosuppression ratios based on age and BMI may minimize cancer risk while improving graft survival and function.
在此，我们对在胰岛移植相关免疫抑制治疗期间伴有移植后皮肤癌的情况下，他克莫司占西罗莫司与他克莫司联合谷浓度的百分比（他克莫司百分比）进行了特征分析。尽管他克莫司和西罗莫司的谷浓度并无差异（分别为0.79和0.73），但在对年龄、性别、体重指数（BMI）以及霉酚酸酯（MMF）的使用进行校正后，高他克莫司百分比使皮肤癌发生几率增加了1.32倍（P = 0.039）。皮肤癌患者可能年龄更大，但差异不显著（平均差异12岁，P = 0.056），不过年龄与校正后的皮肤癌发生几率增加1.22倍显著相关（P = 0.046）。BMI与皮肤癌呈负相关，校正后的比值比（OR）为0.40（P = 0.022）。高他克莫司百分比（>35）使皮肤癌发生率增加了4.6倍，而在联合治疗中，西罗莫司超过75%会导致胰岛移植功能障碍（IGD）事件/年增加5.2倍。通过根据患者年龄和BMI计算他克莫司百分比的最大安全暴露量（MSE），我们发现超过MSE的累积月数可预测皮肤癌（增加1.20倍，P = 0.003）。超过MSE达1年的个体患皮肤癌的可能性要高9.2倍（P = 0.008）。结果表明，基于年龄和BMI调整免疫抑制比例的策略可能会在提高移植物存活和功能的同时，将癌症风险降至最低。
