307: The Effectiveness of a Standardized Desensitization Protocol in Reducing Calculated Panel Reactive Antibodies (cPRA) in Sensitized Heart Transplant Candidates: Does It Make Sense To Desensitize?

Patel, Jitendra; Kittleson, M.; Reed, Elaine F.; Zhang, Q.; Rajalingam, Raja; Velleca, A.; Stimpson, E.; Burch, C.; Kawano, M.; Davis, Stephen J.

doi:10.1016/j.healun.2009.11.320

Cited by 6 publications

(5 citation statements)

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“…Bortezomib appeared to decrease cPRA in patients refractory to desensitization with IVIG/rituximab and plasmapheresis, thus increasing the chances that an acceptable donor heart would become available for the sensitized patient awaiting heart transplantation. 86 …”

Section: Specific Background Topic Presentationsmentioning

confidence: 99%

Report from a consensus conference on antibody-mediated rejection in heart transplantation

Kobashigawa¹,

Crespo-Leiro

Ensminger

et al. 2011

The Journal of Heart and Lung Transplantation

324

257

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BACKGROUND The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. METHODS The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. RESULTS A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. CONCLUSIONS The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues.

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Section: Specific Background Topic Presentationsmentioning

confidence: 99%

Report from a consensus conference on antibody-mediated rejection in heart transplantation

Kobashigawa¹,

Crespo-Leiro

Ensminger

et al. 2011

The Journal of Heart and Lung Transplantation

324

257

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“…By also causing significant decrease in CD138+ cells, it results in a decrease in antibodies to Human Leukocyte Antigen. Bortezomib has been used successfully in two patients undergoing cardiac transplantation in combination with Rituximab and intravenous immunoglobulin to decrease levels of antibodies to Human Leukocyte Antigen before transplantation 25 . Bortezomib is a promising agent in the field of transplantation, as it targets the antibody producing plasma cells.…”

Section: Bortezomibmentioning

confidence: 99%

Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies

et al. 2011

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Highly sensitised children in need of cardiac transplantation have overall poor outcomes because of increased risk for dysfunction of the cardiac allograft, acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac allograft. Cardiopulmonary bypass and the frequent use of blood products in the operating room and cardiac intensive care unit, as well as the frequent use of homografts, have predisposed potential recipients of transplants to allosensitisation. The expansion in the use of ventricular assist devices and extracorporeal membrane oxygenation has also contributed to increasing rates of allosensitisation in candidates for cardiac transplantation. Antibodies to Human Leukocyte Antigen can be detected before transplantation using several different techniques, the most common being the "complement-dependent lymphocytotoxicity assays". "Solid-phase assays", particularly the "Luminex® single antigen bead method", offer improved specificity and more detailed information regarding specificities of antibodies, leading to improved matching of donors with recipients. Allosensitisation prolongs the time on the waiting list for potential recipients of transplantation and increases the risk of complications and death after transplantation. Aggressive reduction of antibodies to Human Leukocyte Antigen in these high-risk patients is therefore of vital importance for long-term survival of the patient and cardiac allograft. Strategies to decrease Panel Reactive Antibody or percent reactive antibody before transplantation include plasmapheresis, intravenous administration of immunoglobulin, and specific treatment to reduce B-cells, particularly Rituximab. These strategies have resulted in varying degrees of success. Antibody-mediated rejection and cardiac allograft vasculopathy are two of the most important complications of transplantation in patients with high Panel Reactive Antibody. The treatment of antibody-mediated rejection in recipients of cardiac transplants is largely empirical and includes the use of high-dose corticosteroids, plasmapheresis, intravenous administration of immunoglobulins, anti-thymocyte globulin, and Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic complement-mediated endothelial injury and chronic vascular rejection. The use of proliferation signal inhibitors, such as sirolimus and everolimus, has been shown to delay the progression of cardiac allograft vasculopathy. In some non-sensitised recipients of cardiac transplants, the de novo formation of antibodies to Human Leukocyte Antigen after transplantation may increase the likelihood of adverse clinical outcomes. The use of serial testing for donor-specific antibodies after cardiac transplantation may be advisable in patients with frequent episodes of rejection and patients with history of sensitisation. Allosensitisation before transplantation can negatively influence outcomes after transplantation. A high incidence of antibody-mediated rejection and graft vasculopathy can result in graft fai...

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“…Only one case report has been published that describes the efficacy of bortezomib for refractory AMR in a cardiac transplant recipient (Eckman et al, 2009). Likewise, only one case series of 7 patients has been reported that describes the successful use of bortezomib for desensitization in candidates refractory to traditional therapies (Patel et al, 2010). The use of bortezomib is likely to expand in cardiac transplantation; particularly as longer-term safety data emerges.…”

Section: Plasma Cell Targeted Agentsmentioning

confidence: 99%

Antibody Mediated Rejection of the Cardiac Allograft

Ensor¹,

Doligalski²

2012

Cardiac Transplantation

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307: The Effectiveness of a Standardized Desensitization Protocol in Reducing Calculated Panel Reactive Antibodies (cPRA) in Sensitized Heart Transplant Candidates: Does It Make Sense To Desensitize?

Cited by 6 publications

References 0 publications

Report from a consensus conference on antibody-mediated rejection in heart transplantation

Report from a consensus conference on antibody-mediated rejection in heart transplantation

Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies

Antibody Mediated Rejection of the Cardiac Allograft

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