Early outcomes for low-risk pediatric heart transplant recipients and steroid avoidance: A multicenter cohort study (Clinical Trials in Organ Transplantation in Children - CTOTC-04)

Lamour, Jacqueline M.; Mason, Kristen; Hsu, Daphne T.; Feingold, Brian; Blume, Elizabeth D.; Canter, Charles E.; Dipchand, Anne I.; Shaddy, Robert E.; Mahle, William T.; Zuckerman, Warren A.; Bentlejewski, Carol; Morrison, Yvonne; Diop, H.; Iklé, David; Odim, Jonah; Zeevi, Adriana; Webber, Steven A.; investigators, Ctotc

doi:10.1016/j.healun.2019.06.006

Cited by 17 publications

(20 citation statements)

References 29 publications

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“…In our later era, we report a 31% risk of rejection among all patients and 37% when eliminating infants from the analysis. The recent CTOTC‐04 multicenter trial reported a 31% risk of acute rejection in the first‐year post‐transplant in a “low‐risk” subset of non‐infant patients using a protocol of ATG induction and steroid avoidance 5 . Another single‐center study reported a 41% one‐year rejection rate using ATG induction 17 …”

Section: Discussionmentioning

confidence: 99%

“…Third, as mentioned above, our ability to risk‐stratify patients into high and low rejection risk may be limited. For example, black race has traditionally been associated with increased risk of early graft loss, 22 but recent multicenter data from the CTOTC‐04 trial (ATG induction) show increased rejection in non‐black patients 5 . Other modes of risk stratification such as degree of donor‐recipient human leukocyte antigen mismatch should be studied with respect to induction and immunosuppression needs 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Immunosuppression (other than induction) was largely the same with tacrolimus, mycophenolate mofetil, and steroids. However, a shorter duration of steroids is used currently based on evidence that steroid avoidance regimens have similar outcomes 5,25,26 . Some later era patients were also changed to the TEAMMATE trial at 6 months instead of the standard immunosuppression regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Induction improves survival and decreases rejection in pediatric heart transplant recipients 2‐4 . Anti‐thymocyte globulin (ATG), a polyclonal antibody, is currently the most widely used induction agent in children, even representing standard induction in the multicenter Clinical Trials in Organ Transplantation in Children (CTOTC) study 5 . Basiliximab (BAS), an IL‐2 receptor antagonist, is another induction agent used in a minority of patients and is generally administered after cardiopulmonary bypass though some evidence may favor pre‐bypass dosing 6 .…”

Section: Introductionmentioning

confidence: 99%

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Impact of induction strategy change on first‐year rejection in pediatric heart transplantation at a single center—From postoperative basiliximab to either postoperative anti‐thymocyte globulin or preoperative basiliximab

Sisson

Padilla

Hubbard

et al. 2021

Clinical Transplantation

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Background Our pediatric heart transplant center transitioned from post‐bypass basiliximab (BAS) induction to either anti‐thymocyte globulin (ATG) or pre‐bypass BAS. The purpose of this study was to compare first‐year rejection rates before and after this change. Methods A single‐center retrospective analysis was conducted of pediatric heart transplant recipients from 2010 to 2019. Primary outcome was first‐year rejection. Bivariate analysis, Kaplan‐Meier curves, and multivariable regression were performed across eras. Results Forty‐three early era patients (55%) received post‐bypass BAS, and 35 late era patients (45%) received pre‐bypass BAS (n = 17) or ATG (n = 18). First‐year rejection decreased in the late era (31% vs 53%, p = .05). This finding was more pronounced after excluding infants (38% vs 73%, p = .006). Late era was associated with a decreased likelihood of rejection (all cohort OR 0.19, 95% CI 0.05‐0.66; infants excluded OR 0.17, 95% CI 0.04‐0.61). No differences in post‐transplant lymphoproliferative disease, donor‐specific antibody, or infection were observed. Conclusions Fewer late era patients receiving ATG or pre‐bypass BAS induction had first‐year rejection compared to the early era patients receiving standard post‐bypass BAS induction. This programmatic shift in induction strategy was readily achievable and potentially effective in reducing first‐year rejection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of induction strategy change on first‐year rejection in pediatric heart transplantation at a single center—From postoperative basiliximab to either postoperative anti‐thymocyte globulin or preoperative basiliximab

Sisson

Padilla

Hubbard

et al. 2021

Clinical Transplantation

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“…Comparing to long-term steroid users (GC use for more than 5 years after transplantation), 10-year patient survival was significantly higher among early (GC discontinuation between 2 to 5 years after transplantation) or late (GC discontinuation after year 5 of transplant) steroid withdrawal (73%, 82% and 80%, respectively) [3] . Steroid discontinuation during 1 week after transplantation has also been applied in low-risk heart transplant pediatrics with acceptable 1-year outcomes [17] .…”

Section: Gcs As Induction and Maintenance Immunosuppressive Therapymentioning

confidence: 99%

Current Status of Glucocorticoid Usage in Solid Organ Transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

Preprint

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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