Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients

Adam Kaplan; Jo-Anne H Young; Raja Kandaswamy; Danielle Berglund; Bettina M Knoll; Gretchen Sieger; Winston Cavert; Arthur Matas; Karam M Obeid

doi:10.1155/2020/8883183

Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients

Can J Infect Dis Med Microbiol. 2020 Oct 9:2020:8883183. doi: 10.1155/2020/8883183. eCollection 2020.

Authors

Adam Kaplan¹, Jo-Anne H Young², Raja Kandaswamy³, Danielle Berglund⁴, Bettina M Knoll⁵, Gretchen Sieger⁴, Winston Cavert², Arthur Matas³, Karam M Obeid²

Affiliations

¹ University of Minnesota, School of Public Health, Division of Biostatistics, Minneapolis, Minnesota 5455, USA.
² University of Minnesota, Department of Medicine, Division of Infectious Diseases and International Medicine, Minneapolis, Minnesota 55455, USA.
³ University of Minnesota, Department of Surgery, Minneapolis, Minnesota 55455, USA.
⁴ University of Minnesota, Clinical and Translational Science Institute, Minneapolis, Minnesota 55455, USA.
⁵ New York Medical College, Department of Medicine, Valhalla, New York 10595, USA.

Abstract

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), P=0.01), bacterial infections (HR 1.33 (1.05-1.67), P=0.02), fungal infections (HR 1.86 (1.28-2.71), P < 0.01), and cytomegalovirus infections (HR 2.29 (1.39-3.77), P < 0.01). In addition, EAE was associated with higher risk of acute cellular rejection (HR 2.09 (1.46-2.99), P < 0.01). 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.