Multiple doses of alemtuzumab for immunosuppressive therapy of patients with hematologic malignancies and hematopoietic stem cell transplant have been associated with a high rate of infection. In transplantation, limited alemtuzumab dosing has been successfully used as induction immunosuppression. The effect of multiple doses of alemtuzumab, used as maintenance therapy to minimize steroid and/or calcineurin inhibitor toxicity in solid organ transplant recipients, is unknown. We evaluated the infectious and noninfectious outcomes of 179 pancreas transplant recipients treated with alemtuzumab for induction and maintenance therapy (extended alemtuzumab exposure (EAE)) from 2/28/2003 through 8/31/2005, compared with 159 pancreas transplant recipients with standard induction and maintenance (SIM) therapy performed before (1/1/2002 until 12/31/2002) and after (1/1/2006 until 12/31/2006) the implementation of EAE. EAE was associated with higher risk of overall infections (hazard ratio (HR) 1.33 (1.06–1.66), ), bacterial infections (HR 1.33 (1.05–1.67), ), fungal infections (HR 1.86 (1.28–2.71), ), and cytomegalovirus infections (HR 2.29 (1.39–3.77), ). In addition, EAE was associated with higher risk of acute cellular rejection (HR 2.09 (1.46–2.99), ). In conclusion, while a limited alemtuzumab dosing is safe and effective for induction therapy in pancreas transplantation, EAE combined with steroid and calcineurin minimization is associated with a high risk of infectious complications and acute cellular rejection.

中文翻译：

---

每月Alemtuzumab作为胰腺移植受者的钙调神经磷酸酶抑制剂和类固醇免费方案的长期感染性和非感染性结果

多剂量的alemtuzumab用于血液恶性肿瘤患者的免疫抑制治疗和造血干细胞移植与高感染率相关。在移植中，有限的alemtuzumab剂量已成功用于诱导免疫抑制。未知的多剂量alemtuzumab在维持器官器官移植受者中用作维持治疗以最大程度降低类固醇和/或钙调神经磷酸酶抑制剂毒性的作用。我们评估了2003年2月28日至2005年8月31日接受179例接受alemtuzumab诱导和维持治疗（扩大的alemtuzumab暴露量（EAE））的胰腺移植受者的感染性和非感染性结果，与159例接受EAE实施之前（1/1/2002至12/31/2002）和之后（1/1/2006至12/31/2006）进行标准诱导和维持（SIM）治疗的胰腺移植受者进行比较。EAE与总体感染风险较高相关（危险比（HR）1.33（1.06-1.66），），细菌感染（HR 1.33（1.05-1.67），），真菌感染（HR 1.86（1.28–2.71），）和巨细胞病毒感染（HR 2.29（1.39–3.77），）。此外，EAE与急性细胞排斥反应的风险较高相关（HR 2.09（1.46-2.99），）。总之，尽管有限的阿仑单抗剂量对胰腺移植的诱导治疗是安全有效的，但EAE结合类固醇和钙调神经磷酸酶的最小化与感染并发症和急性细胞排斥的高风险相关。