Safety and efficacy of alemtuzumab in the treatment of late acute renal allograft rejection

Upadhyay, Kiran; Midgley, Laurie; Moudgil, Asha

doi:10.1111/j.1399-3046.2011.01615.x

Cited by 17 publications

(9 citation statements)

References 38 publications

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“…Similar results were previously reported for kidney transplantation [2, 3]. Therefore, we hypothesized that NK cells have an important role in resisting microbial attack during alemtuzumab induction for several months while T-cells repopulate.…”

Section: Introductionsupporting

confidence: 82%

“…CD52 is a glycoprotein expressed on approximately 95% of peripheral blood lymphocytes, natural killer (NK) cells, monocytes, macrophages, and thymocytes [1]. Lymphocyte depletion is expected to increase the risk of opportunistic infections [2, 3]. However, some studies have shown that the frequency of infectious diseases does not increase after organ transplantation [4–10].…”

Section: Introductionmentioning

confidence: 99%

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CD52-Negative NK Cells Are Abundant in the Liver and Less Susceptible to Alemtuzumab Treatment

et al. 2016

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BackgroundT-cell depleting strategies have become an integral part of immunosuppressive regimens in organ transplantation. Alemtuzumab is a humanized monoclonal antibody against CD52, a cell-surface antigen on several immune cells. It has been suggested that lymphocyte depletion increases the risk of serious infections. However, this has not been observed with short-term alemtuzumab treatment in an organ transplant setting. For induction therapy using alemtuzumab following liver transplantation, we found that T- and B-cell numbers declined rapidly after alemtuzumab therapy; however, the natural killer (NK) cell number was sustained. NK cells are important effectors of innate immunity. Since the effects of alemtuzumab on NK cell functions, especially those of liver NK cells, are unknown, this study aimed to investigate this in detail.MethodsTo assess the effect of alemtuzumab on NK cells, samples were obtained from 7 organ donors and examined by flow cytometry using Annexin V and propidium iodide. Phenotypical and functional differences within subsets of NK cells with different levels of CD52 expression were determined by flow cytometry and in vitro cytotoxicity assays.ResultsCD52 expression on NK cells was lower than that on other lymphocyte subsets. The liver contained a large number of CD52− NK cells compared with the peripheral blood. In vitro treatment of liver-derived NK cells with alemtuzumab did not result in cell death. In contrast, co-incubation with alemtuzumab induced cell death in peripheral blood mononuclear cells and non-NK cells in the liver. Furthermore, CD52− liver NK cells were more cytotoxic and produced more IFN-γ than CD52+ NK cells after cytokine activation.ConclusionThe liver contains a large number of CD52− NK cells. These cells are refractory to alemtuzumab and have robust activity. These findings indicate that CD52− NK cells persist and could protect against infection after alemtuzumab-based lymphocyte depletion.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

CD52-Negative NK Cells Are Abundant in the Liver and Less Susceptible to Alemtuzumab Treatment

et al. 2016

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“…Alemtuzumab is currently registered for the treatment of chronic lymphatic leukemia but data on the safety and efficacy of treatment of acute rejection after organ transplantation are scarce. Several studies reported the results in small groups of patients, merely demonstrating that recurrent or steroid-resistant rejection can be reversed with alemtuzumab (6)(7)(8)(9)(10). Randomized trials comparing alemtuzumab with other T cell-depleting agents for the treatment of acute rejection have not been performed.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Steroid-Resistant Acute Renal Allograft Rejection With Alemtuzumab

Hoogen

Hesselink

Son

et al. 2013

American Journal of Transplantation

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Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (15-30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5-4.0 mg/kg bodyweight i.v. for 10-14 days; n = 20). We assessed treatmentfailure (graft loss, lack of improvement of graft function or need for additional anti-rejection treatment), infections during the first 3 months after treatment and infusion-related side effects. In both groups, the median time-interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff-IIA or higher. Three alemtuzumab-treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion-related side-effects in three alemtuzumabtreated patients (27%), and more severe infusionrelated side effects in 17 RATG-treated patients (85%, p = 0.013). Drug related costs of alemtuzumabtreatment were lower than of RATG-treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid-resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion-related side-effects. These data warrant a prospective trial.

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“…In the previous issue of Pediatric Transplantation , Upadhyay et al. (1) describe three patients who are falling into the very unfortunate category described earlier. Specifically, they summarize their experience using alemtuzumab (Campath) as a last‐resort treatment option in late kidney transplant rejection in two teenagers, both with a reported history of non‐adherence and one younger child with a number of apparent oddities potentially contributing to the patient’s difficulties with rejections as well as infectious and other complications, for example, diarrhea, hypersplenism secondary to underlying autosomal recessive polycystic kidney disease, leukopenia and diarrhea in the first post‐transplant month leading to discontinuation of mycophenolate, and melatonin therapy.…”

mentioning

confidence: 95%