Impact of Left Venticular Assist Device (LVAD)-mediated Humoral Sensitization on Post-transplant Outcomes

Joyce, David L.; Southard, Robert E.; Torre‐Amione, Guillermo; Noon, George P.; Land, Geoffrey A.; Loebe, Matthias

doi:10.1016/j.healun.2005.06.028

Cited by 83 publications

(64 citation statements)

References 18 publications

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“…The incidence of HLA mismatch !4 antigens was increased in the patients that died from CAV when compared to the general population, but the degree of sensitization at the time of transplant, as indicated by PRA measurements and desensitization strategies (Table 1 and data not shown), was comparable. It is known that implantation of an LVAD increases humoral sensitization; however, there appears to be no association between LVAD implantation and negative events such as rejection and CAV [17][18][19][20][21][22], perhaps due to stringent immunosuppression regimens [5].…”

Section: Discussionmentioning

confidence: 99%

One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation☆

Robertson

Lober

Smedira

et al. 2008

European Journal of Cardio-Thoracic Surgery

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Section: Discussionmentioning

confidence: 99%

One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation☆

Robertson

Lober

Smedira

et al. 2008

European Journal of Cardio-Thoracic Surgery

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“…1 The increased use of ventricular assist devices as a bridge to cardiac transplantation also sensitizes these candidates to MHC alloantigens prior to transplantation. 5 Methods to prevent sensitization would therefore have a broad therapeutic impact. 3 The power of MHC-specific antibodies to destroy vascularized allografts within minutes following transplantation has been appreciated since 1969.…”

Section: Introductionmentioning

confidence: 99%

Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization

Yan

Huang

et al. 2008

Blood

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Sensitization is a critical unresolved challenge in transplantation. We show for the first time that blockade of CD154 alone or combined with T-cell depletion prevents sensitization. Allogeneic skin grafts were rejected by recipients treated with anti-␣␤ T-cell receptor (TCR), anti-CD154, anti-OX40L, or anti-inducible costimulatory pathway (ICOS) mAb alone with a kinetic similar to untreated recipients. However, the production of anti-donor MHC antibody was prevented in mice treated with anti-CD154 mAb only, suggesting a specific role for the CD154-CD40 pathway in B-cell activation. The impairment of T celldependent B-cell responses by blocking CD154 occurs through inhibiting activation of T and B cells and secretion of IFN-␥ and IL-10. Combined treatment with both anti-CD154 and anti-␣␤ TCR abrogated antidonor antibody production and resulted in prolonged skin graft survival, suggesting the induction of both T-and B-cell tolerance with prevention of allogeneic sensitization. In addition, we show that the tolerance induced by combined treatment was nondeletional. Moreover, these sensitization-preventive strategies promote bone marrow engraftment in recipients previously exposed to donor alloantigen. These findings may be clinically relevant to prevent allosensitization with minimal toxicity and point to humoral immunity as playing a dominant role in alloreactivity in sensitized recipients. IntroductionSensitization of patients to major histocompatibility complex (MHC) antigens is among the most critical challenges in clinical transplantation. [1][2][3] Patients with preformed antibodies have higher rejection rates and inferior outcomes for bone marrow transplantation (BMT) and organ transplantation. Most patients with sickle cell disease and thalassemia who are candidates for BMT are sensitized due to chronic transfusion therapy. 4 Similarly, in solid organ transplantation, allorejection mediated by preformed antibodies has recently been recognized as a major cause of graft loss in sensitized patients. Although 20% of candidates for renal transplantation are sensitized, they receive less than 3% of available organs. 1 The increased use of ventricular assist devices as a bridge to cardiac transplantation also sensitizes these candidates to MHC alloantigens prior to transplantation. 5 Methods to prevent sensitization would therefore have a broad therapeutic impact. 3 The power of MHC-specific antibodies to destroy vascularized allografts within minutes following transplantation has been appreciated since 1969. 6,7 Immunosuppressive drugs have been used to reduce the antibody response to allografts, 8,9 but the toxicity associated with the chronic use of these drugs is a significant limitation. Moreover, long-term outcomes are still significantly inferior. 10 Induction of mixed allogeneic chimerism has been demonstrated to confer donor-specific tolerance in the setting of allosensitization. 8,11 However, to establish mixed chimerism in sensitized recipients, the immune barrier from allosensitization must be overco...

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“…13 VAD therapy is associated with frequent complications, including but not limited to renal failure, infection, sensitization, and thromboembolism, which may increase the risk of posttransplantation adverse events. [14][15][16][17] The benefits and risks associated with HTx and VAD therapy in addition to the lack of comparative studies on these therapies make it difficult to confidently determine which approach is best on the basis of individual patient characteristics. In this setting, decision analytic models may be useful to assist clinical decision making.…”

Section: Editorial See P 2375 Clinical Perspective On P 2435mentioning

confidence: 99%

Cost-Effectiveness of Ventricular Assist Device Therapy as a Bridge to Transplantation Compared With Nonbridged Cardiac Recipients

Alba

Delgado

et al. 2013

Circulation

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Background-Current available treatment options for advanced heart failure include heart transplantation and ventricular assist device (VAD) therapy. This project aimed to evaluate the cost-effectiveness of a bridge-to-transplantation (BTT)-VAD approach relative to direct heart transplantation in transplant-eligible patients. Methods and Results-A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients' baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio. Conclusions-BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonlyaccepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances. (Circulation. 2013;127:2424-2435.)Key Words: cost-benefit analysis ◼ economics ◼ heart-assist devices ◼ heart failure ◼ heart transplantation © 2013 American Heart Association, Inc.

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Impact of Left Venticular Assist Device (LVAD)-mediated Humoral Sensitization on Post-transplant Outcomes

Cited by 83 publications

References 18 publications

One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation☆

One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation☆

Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization

Cost-Effectiveness of Ventricular Assist Device Therapy as a Bridge to Transplantation Compared With Nonbridged Cardiac Recipients

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