Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation1

Cherikh, Wida S.; Kauffman, H. Myron; McBride, Maureen; Maghirang, Jude; Swinnen, Lode J.; Hanto, Douglas W.

doi:10.1097/01.tp.0000100826.58738.2b

Cited by 281 publications

(229 citation statements)

References 26 publications

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“…14 Apart from the association of anti-CD3 mAbs with posttransplantation lymphoproliferative disease, 15 the clinical evidence for one treatment regimen over another in reducing posttransplantation malignancy is varied and not compelling. This analysis suggests that longer term follow-up of recent comparative immunosuppressive trials (e.g., Efficacy Limiting Toxicity Elimination [ELITE]-Symphony Trial 13 ) could provide important data on cancer outcomes and that better markers of the degree of immunosuppression may also aid in reducing cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

Gallagher¹,

Kelly²,

Jardine³

et al. 2010

Journal of the American Society of Nephrology

184

121

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Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin cancer (excluding melanoma) for 481 patients during a median follow-up of 20.6 years. A total of 226 patients developed at least one cancer: 95 with non-skin cancer and 171 with skin cancer. In the intention-to-treat analysis, mean times to first non-skin cancer (16.0, 15.3, and 15.7 years for groups 1 through 3, respectively) and first skin cancer (13.6, 14.3, and 15.2 years, respectively) were not different among the three groups or between any subgroup. In multivariate analyses, non-skin cancer associated with increasing age and previous smoking history, whereas skin cancer associated with increasing age, nonbrown eye color, fairer skin, and a functioning transplant. Treatment allocation did not associate with development of either form of cancer in multivariate analyses. In conclusion, these immunosuppressive regimens, widely used in recent decades, carry similar risks for carcinogenicity after kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

Gallagher¹,

Kelly²,

Jardine³

et al. 2010

Journal of the American Society of Nephrology

184

121

View full text Add to dashboard Cite

show abstract

“…[12][13][14] OKT3, recognizing CD3, the T-cell lineage marker, is more specific and highly effective, but is associated with severe side effects such as cytokine release syndrome, pulmonary oedema, aseptic meningitis and EBV-related post-transplant lymphoproliferative disease. [15][16][17][18] Although preemptive corticosteroids mitigate some of these effects, production of OKT3 was discontinued.…”

Section: Introductionmentioning

confidence: 99%

Selective, efficient modulation of activated CD4+ αβT cells by the novel humanized antibody GZ-αβTCR targeting human αβTCR

Blank

Welker

Haarer

et al. 2014

Bone Marrow Transplant

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Allograft rejection and immunosuppression are two major issues in transplantation medicine. The specific targeting of alloreactive T cells, the initiators and promoters of allograft rejection, would be a promising strategy to reduce unwanted T-cell responses and side effects of lifelong immunosuppression. The novel humanized monoclonal antibody GZ-αβTCR, specific for the human αβT-cell receptor, was tested in vitro and in vivo for its specificity and efficacy to modulate the αβT-cell compartment. GZ-αβTCR moderately induced apoptosis in resting αβT cells in vitro, an effect considerably amplified in activated T cells. A single dose of GZ-αβTCR significantly reduced human CD45 + CD3 + T cells in vivo, with a preferential modulation of CD4 + αβT cells. Importantly, naive T cells, the T-cell subset from which alloreactivity emanates, were significantly reduced. Simultaneously, a significant, compensatory increase of γδ T cells was observed in vitro and in vivo in both humanized mouse models examined. GZ-αβTCR did not induce cytokines and was well tolerated. Thus, specificity and high efficacy make GZ-αβTCR a powerful tool to selectively eliminate putatively detrimental T-cell subsets, a major goal in transplantation medicine. At the same time, GZ-αβTCR spares γδ and natural killer cells, thus leaving the recipient's immune system competent for cell-mediated immunoregulation and cell-mediated immunity.

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“…Data are even more conflicting when it comes to the use of anti-proliferative agents. Some studies suggest that the use of Mycophenolate Mofetil (MMF) is associated with earlier development of malignancy when compared to Azathioprine (AZA) [23,24], whereas another study conducted by Cherikh et al recognised a lower incidence of PTLD with MMF [25]. Mammalian target of rapamycin (mTOR) inhibitors have been generally associated with the lowest risk.…”

Section: Discussionmentioning

confidence: 99%

De novo papillary carcinoma in a renal allograft: the pros and cons of immunosuppression

2015

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We present a case of a multifocal kidney transplant renal cell carcinoma in a 35-year-old lady, presenting 16 years after kidney transplantation, diagnosed during investigation of recurrent urinary tract infections. The patient underwent a graft nephrectomy and subsequently maintained on haemodialysis. She remained disease-free after 4 years of surveillance and thus reactivated on the transplant list. This case reinforces the fact that immunosuppressive therapy has made kidney transplantation possible; however, it is accompanied by a higher incidence of malignancy. It also reinforces the importance of lifelong screening of both native and renal transplant grafts.

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Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation1

Cited by 281 publications

References 26 publications

Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

Selective, efficient modulation of activated CD4+ αβT cells by the novel humanized antibody GZ-αβTCR targeting human αβTCR

De novo papillary carcinoma in a renal allograft: the pros and cons of immunosuppression

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