Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients

Bank, J.; Heidt, Sebastiaan; Moes, Dirk Jan A R; Roelen, Dave L.; Mallat, M.; Boog, Paul J.M. van der; Vergunst, Manon; Zijde, Cornelia M. Jol–van der; Bredius, R.G.M.; Braat, Andries E.; Ringers, J.; Tol, Maarten J.D. van; Claas, Frans H.J.; Reinders, Marlies E.J.; Fijter, J. W. De

doi:10.1097/txd.0000000000000634

Cited by 11 publications

(15 citation statements)

References 41 publications

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“…Alemtuzumab induced leucopenia usually results in the reduction of MMF dose and, as a result, the mean dose of MMF was 14 mg/kilogram which is significantly lower than those who received either ATG or daclizumab [ 143 ]. KTR with high immunological risk must be monitored for a potential risk of rejection while reducing MMF in such events [ 144 ]. Alemtuzumab has been incriminated in B cell dysregulation and causing autoimmune disorder.…”

Section: Insight Into Etiology Of Hematological Cytopenia and Subsmentioning

confidence: 99%

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Khalil

Khan

et al. 2018

Journal of Transplantation

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Drug-induced hematological cytopenia is common in kidney transplantation. Various cytopenia including leucopenia (neutropenia), thrombocytopenia, and anemia can occur in kidney transplant recipients. Persistent severe leucopenia or neutropenia can lead to opportunistic infections of various etiologies. On the contrary, reducing or stopping immunosuppressive medications in these events can provoke a rejection. Transplant clinicians are often faced with the delicate dilemma of balancing cytopenia and rejection from adjustments of immunosuppressive regimen. Differentials of drug-induced cytopenia are wide. Identification of culprit medication and subsequent modification is also challenging. In this review, we will discuss individual drug implicated in causing cytopenia and correlate it with corresponding literature evidence.

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Section: Insight Into Etiology Of Hematological Cytopenia and Subsmentioning

confidence: 99%

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Khalil

Khan

et al. 2018

Journal of Transplantation

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“…In kidney transplant alone (KTA), the induction with ATG followed by steroid-free maintenance IS, achieved a graft survival rate similar to that of historical KTA recipients who received the triple maintenance IS with fewer CMV infections, posttransplant diabetes cataract, and avascular necrosis when compared to historical controls with the same induction IS but receiving the triple maintenance IS [ 20 , 21 ]. Similarly, steroid-free maintenance IS, following induction with alemtuzumab, was associated with favorable graft and adverse events outcomes in KTA [ 8 , 9 , 11 , 12 , 14 ] and SPK recipients [ 12 , 15 , 22 – 26 ] compared to induction with ATG or nonlymphocytes depleting agents, with either triple or prednisone-free maintenance IS. In these studies, the total alemtuzumab doses were 40–60 mg given in 20–30 mg/day.…”

Section: Discussionmentioning

confidence: 99%

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

Kaplan

Young

Kandaswamy

et al. 2020

Canadian Journal of Infectious Diseases and Medical Microbiolog

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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.

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“…ALEM, currently used mainly for the treatment of multiple sclerosis, previously developed as an effective lymphocyte-depleting agent in renal transplantation, is considered effective as induction agent in SPK with results comparable to those for ATG [7–13]. However, little is known about the long-term results [7–13,16,17].…”

Section: Discussionmentioning

confidence: 99%

“…TAC is preferred for maintenance immunosuppression following ALEM induction therapy, since T cells with a memory-like phenotype are dominant following T cell depletion, but sensitive to calcineurin inhibitors [7–11,13,18,19]. Hesitation concerning increased use of ALEM was fueled by contrasting reports about the immunological benefit.…”

Section: Discussionmentioning

confidence: 99%

“…Improved patient and graft survival in simultaneous pancreas-kidney transplantation (SPK) can be achieved with induction therapy [1–6]. Controlled trials comparing the anti-CD52 antibody alemtuzumab (ALEM) and anti-thymocyte globulin (ATG) in SPK report good results for ALEM [7–13]. In contrast to the Euro-SPK study including ATG, reports on long-term outcome in SPK with ALEM remain sparse and long-term immunosuppressive treatment following initial protocol-based therapy has not been addressed [12–15].…”

Section: Introductionmentioning

confidence: 99%

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Good Results with Individually Adapted Long-Term Immunosuppression Following Alemtuzumab Versus ATG Induction Therapy in Combined Kidney-Pancreas Transplantation: A Single-Center Report

et al. 2019

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Retrospective analysis of the long-term results of a randomized controlled trial comparing alemtuzumab (ALEM) and antithymocyte globulin (ATG) as induction therapy in simultaneous pancreas-kidney transplantation (SPK) to address individualized long-term immunosuppression.Between 2006 and 2010 a total of 30 SPKs were randomized to treatment with ALEM plus tacrolimus (TAC) monotherapy (Group A, n=14) versus ATG induction plus TAC, mycophenolate mofetil (MMF) and steroids (Group B, n=16), followed by individualized long-term immunosuppression. We here present the long-term results for graft survival, graft function, and major complications.The 9-year patient survival rates in Groups A and Group B were 92.9% and 86.7% respectively; pancreas graft survival was 75.0% and 65.0% respectively; renal graft survival was 83.1% and 93.8% respectively. Long-term graft function was excellent with a creatinine of 1.5 mg/dL and 1.4 mg/dL, fasting glycemia of 104 mg/dL and 102 mg/dL, hemoglobin (Hb) A1c of 5.4 g% and 5.6 g% in Group A and Group B, respectively. Major complications were comparable in both groups.Good long-term results for patient, pancreas graft and kidney graft survival were achieved in both groups with individually adapted maintenance immunosuppression. ALEM is a valid induction therapy.

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Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients

Abstract: Supplemental digital content is available in the text.

Cited by 11 publications

References 41 publications

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

Drug-Induced Hematological Cytopenia in Kidney Transplantation and the Challenges It Poses for Kidney Transplant Physicians

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

Good Results with Individually Adapted Long-Term Immunosuppression Following Alemtuzumab Versus ATG Induction Therapy in Combined Kidney-Pancreas Transplantation: A Single-Center Report

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