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.
Highlights
In solid organ transplantation (SOT), since 1984, calcineurin inhibitors (CNI) have been the backbone of the maintenance immunosuppressive (IS) therapy; they are, associated with multiple adverse events including nephrotoxicity
We studied the long-term infectious and noninfectious outcomes for recipients treated with this extended dosing of alemtuzumab compared to those in recipients treated without extended use of lymphocyte-depleting agents in the year before and after the extended alemtuzumab dosing period, with a more detailed description of the infectious complications
Following SOT procedures, maintenance IS therapy is essential for graft survival and typically includes a CNI, mycophenolate mofetil (MMF), and prednisone. is, is associated with multiple adverse events
Summary
® Alemtuzumab (Campath-1H, MabCampath ) is a humanized monoclonal antibody directed against CD52, a glycoprotein expressed on circulating T- and B-lymphocytes, monocytes, macrophages, dendritic cells, and NK cells [1, 2]. Infection rates among SOT recipients who received limited alemtuzumab dosing are similar to those who received other lymphocyte depleting agents, such as antithymocyte globulin (ATG), for induction therapy [8, 15,16,17,18]. It is unknown whether SOT recipients receiving multiple doses of alemtuzumab, for both induction and maintenance therapy, would have increased infection rates. We studied the long-term infectious and noninfectious outcomes for recipients treated with this extended dosing of alemtuzumab compared to those in recipients treated without extended use of lymphocyte-depleting agents in the year before and after the extended alemtuzumab dosing period, with a more detailed description of the infectious complications
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