Opportunistic Infections in 547 Organ Transplant Recipients Receiving Alemtuzumab, a Humanized Monoclonal CD-52 Antibody

Peleg, Anton Y.; Husain, Shahid; Kwak, Eun Jeong; Silveira, Fernanda P.; Ndirangu, Magdaline; Tran, Jerry M.; Shutt, Kathleen A.; Shapiro, Ron; Thai, Ngoc; Abu‐Elmagd, Kareem; McCurry, Kenneth R.; Marcos, Amadeo; Paterson, David L.

doi:10.1086/510388

Cited by 248 publications

(150 citation statements)

References 37 publications

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“…Despite the long-lasting CD4 T cell depletion (15) for over 1 year mortality due to infection was not increased in alemtuzumab patients. This finding is somewhat surprising and confirms reports in other publications (16,17) with a lack of opportunistic infections when it was used as induction agent. Similar to data reported by McCurry et al (10,11), none of our patients developed early posttransplant lymphoproliferative disorder (PTLD) despite aggressive T cell depletion.…”

Section: Discussionsupporting

confidence: 85%

Alemtuzumab in Lung Transplantation: An Open-Label, Randomized, Prospective Single Center Study

Jaksch

Ankersmit

Scheed

et al. 2014

American Journal of Transplantation

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Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ! A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p ¼ 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

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Section: Discussionsupporting

confidence: 85%

Alemtuzumab in Lung Transplantation: An Open-Label, Randomized, Prospective Single Center Study

Jaksch

Ankersmit

Scheed

et al. 2014

American Journal of Transplantation

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“…There is a case of B. mandrillaris infection described in a series documenting opportunistic infections in the posttransplant period (287).…”

Section: Other Parasitic Infectionsmentioning

confidence: 99%

Transmission of Tropical and Geographically Restricted Infections during Solid-Organ Transplantation

et al. 2008

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SUMMARY In recent years, the increasing number of donors from different regions of the world is providing a new challenge for the management and selection of suitable donors. This is a worldwide problem in most countries with transplantation programs, especially due to the increase in immigration and international travel. This paper elaborates recommendations regarding the selection criteria for donors from foreign countries who could potentially transmit tropical or geographically restricted infections to solid-organ transplant recipients. For this purpose, an extensive review of the medical literature focusing on viral, fungal, and parasitic infections that could be transmitted during transplantation from donors who have lived or traveled in countries where these infections are endemic has been performed, with special emphasis on tropical and imported infections. The review also includes cases described in the literature as well as risks of transmission during transplantation, microbiological tests available, and recommendations for each infection. A table listing different infectious agents with their geographic distributions and specific recommendations is included.

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“…mune dysfunction is particularly intense with the use of lymphocytedepleting drugs, as either induction or re jection therapy, such as muromonabCD3 (OKT3) and antithymocyte globulin [37,38] . When alemtuzumab, an antiCD52 lymphocytic antibody, is used for shortcour se induction therapy only, the risk of developing CMV disease is low [39,40] . However, when patients receive alem tuzumab as rejection therapy, the risk of developing CMV disease is higher, suggesting that rejection per se also in creases the risk [40] .…”

Section: Drug-induced Immunodeficiencymentioning

confidence: 99%

“…When alemtuzumab, an antiCD52 lymphocytic antibody, is used for shortcour se induction therapy only, the risk of developing CMV disease is low [39,40] . However, when patients receive alem tuzumab as rejection therapy, the risk of developing CMV disease is higher, suggesting that rejection per se also in creases the risk [40] . Basiliximab and daclizumab are also used for induction therapy and they act as antiCD25 directed nondepleting antibodies (interleukin2 receptor antagonist).…”

Section: Drug-induced Immunodeficiencymentioning

confidence: 99%

Current concepts on cytomegalovirus infection after liver transplantation

Lee

Razonable

2010

WJH

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Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly asso ciated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall pa tient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver trans plant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the preven tion of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R-liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, val ganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to mo derate CMV disease in solid organ (including liver) tran splant recipients. In this article, the authors review the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

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Opportunistic Infections in 547 Organ Transplant Recipients Receiving Alemtuzumab, a Humanized Monoclonal CD-52 Antibody

Abstract: Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.

Cited by 248 publications

References 37 publications

Alemtuzumab in Lung Transplantation: An Open-Label, Randomized, Prospective Single Center Study

Alemtuzumab in Lung Transplantation: An Open-Label, Randomized, Prospective Single Center Study

Transmission of Tropical and Geographically Restricted Infections during Solid-Organ Transplantation

Current concepts on cytomegalovirus infection after liver transplantation

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