Induction Therapy With Thymoglobulin After Heart Transplantation: Impact of Therapy Duration on Lymphocyte Depletion and Recovery, Rejection, and Cytomegalovirus Infection Rates

Goland, Sorel; Czer, L.; Coleman, Bernice; Robertis, Michele A. De; Mirocha, James; Zivari, Kaveh; Schwarz, Ernst R.; Kass, Robert M.; Trento, Alfredo

doi:10.1016/j.healun.2008.07.002

Cited by 36 publications

(22 citation statements)

References 21 publications

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“…The ATG dose in the Mattei study was 2.5 mg/kg/d for 3‐5 days, a total dose of 7.5‐12.5 mg/kg, while our median total dose was 3.4 mg/kg . Interestingly, Goland et al analyzed two different dosing regimens of Thymoglobulin ® (1.5 mg/kg for 5 days versus 7 days) and found significantly less rejection at 1‐year with the 7‐day regimen without increases in CMV infection …”

Section: Discussionmentioning

confidence: 68%

Incidence of cytomegalovirus in cardiac transplant recipients receiving induction immunosuppression with antithymocyte globulin

Jewani

Pouch

Kissling

2018

Clinical Transplantation

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Background: Cytomegalovirus (CMV) is a major cause of morbidity and mortality in cardiac transplant recipients. Use of induction immunosuppression in cardiac transplantation may have an impact on the incidence of CMV, but literature is limited. Methods: Single-center, retrospective cohort study comparing the risk of CMV infection and disease in cardiac transplant patients receiving antithymocyte globulin (ATG) induction therapy to those receiving no antibody induction. Results: A total of 75 patients were included in our analysis, 50 who received ATG induction and 25 who did not. CMV infection occurred in 10 (20%) and 5 (20%) patients in the ATG and No ATG groups, respectively (P > 0.99). CMV disease occurred in 10 (20%) and 4 (16%) patients in the ATG and No ATG groups, respectively (P = 0.763). The median time from transplant to CMV infection was 200.0 [142.5, 364.5] days in the ATG group vs 221.0 [192.0, 299.0] days in the No ATG group (P = 0.723). The median time from end of CMV prophylaxis to CMV infection was 94.5 [66.5, 151.0] days in the ATG group vs 53.0 [41.0,149.5] days in the No ATG group (P = 0.202). Freedom from CMV infection was highest in the D+/R+ group and lowest in the D+/R− group.Conclusion: In cardiac transplant recipients, ATG induction was not associated with an increased incidence of CMV infection or disease in the setting of valganciclovir prophylaxis and an initial maintenance immunosuppression regimen of primarily steroids, mycophenolate mofetil, and tacrolimus. K E Y W O R D Santithymocyte globulin, cytomegalovirus, heart transplant, induction 2 of 7 | JEWANI Et Al.

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Section: Discussionmentioning

confidence: 68%

Incidence of cytomegalovirus in cardiac transplant recipients receiving induction immunosuppression with antithymocyte globulin

Jewani

Pouch

Kissling

2018

Clinical Transplantation

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“…assessed a shorter course of rATG (ATG‐Fresenius), with a single high intraoperative dose followed by 1.5 mg/kg for 5 days ( n = 14), and observed similar efficacy to a standard 7‐day course ( n = 16) . It appears that the early high dose is necessary to maintain efficacy, however, since a fixed dose of 1.5 mg/kg for 5 days alone may offer less effective rejection prophylaxis than 7 days . A more promising strategy may be to individualize rATG dosing with the aim of maintaining lymphocyte count at 100/μl or higher .…”

Section: Clinical Considerationsmentioning

confidence: 98%

“…When using rATG induction, it should be borne in mind that dosing regimens have evolved over the last decade, both in kidney and heart transplantation . Faggian et al .…”

Section: Clinical Considerationsmentioning

confidence: 99%

“…When using rATG induction, it should be borne in mind that dosing regimens have evolved over the last decade, both in kidney [34] and heart transplantation [39,[60][61][62]. Faggian et al assessed a shorter course of rATG (ATG-Fresenius), with a single high intraoperative dose followed by 1.5 mg/kg for 5 days (n = 14), and observed similar efficacy to a standard 7-day course (n = 16) [39].…”

Section: Dosing and Safety Issuesmentioning

confidence: 99%

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Induction therapy in heart transplantation: where are we now?

et al. 2013

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Summary Although induction therapy has been used in heart transplantation for many years, its role has not been fully elucidated. Early safety concerns relating to OKT3 or intensive lymphocyte‐depleting regimens have largely been addressed by modern induction protocols using rabbit antithymocyte globulin (rATG [Thymoglobuline® or ATG‐Fresenius]) and interleukin‐2 receptor antagonist (IL‐2RA) agents, but although the number of randomized controlled studies has expanded there are still gaps in the evidence base. Rejection prophylaxis may be somewhat more effective with rATG than IL‐2RA agents, but this has not been proven conclusively. Administration of induction therapy to support delayed introduction of calcineurin inhibitors in patients at risk of renal dysfunction is relatively well documented and widely used. Increasingly, it is recognized that sensitized patients and individuals with primary graft function are suitable candidates for induction therapy, and the possibility that rATG may inhibit cardiac allograft vasculopathy is also of considerable interest. Until the question of whether rATG is associated with increased risk of infection, routine prophylaxis is advisable. IL‐2RA induction has an excellent safety profile. Dosing rATG according to lymphocyte count reduces cumulative dose without compromising efficacy. Further controlled trials are required to determine when and how to deploy induction most effectively following heart transplantation.

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“…In recent years, investigators have focused on using antithymocyte globulin (ATG) over a shorter duration (5 vs. 7 days) or adapted to lymphocyte counts (<100/ml) [11,12]. Whereas shorter duration was associated with higher rejection rates, ATG doses adapted to T-cell counts was associated with lower rejection rates as well less ATG doses.…”

Section: Survival and Rejection Polyclonal Antibodiesmentioning

confidence: 99%