Sensitization following Thymoglobulin and Atgam rejection therapy as determined with a rapid enzyme-linked immunosorbent assay

Regan, John F.; Campbell, Kevin; Smith, Le Van; Schroeder, Timothy; Womble, D.; Kano, J.M; Buelow, Roland

doi:10.1016/s0966-3274(99)80028-8

Cited by 18 publications

(14 citation statements)

References 9 publications

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“…In solid organ transplant recipients, presensitization to ATG did not appear to adversely affect efficacy, 21 which supports use of ATG in skin test-positive patients. In addition, the steroid and antihistamine premedications used by most centers might ameliorate any potential side-effects from administration of the therapeutic dose of ATG in the face of a positive skin test.…”

Section: Discussionmentioning

confidence: 71%

Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey

Hsu

May

Carrum

et al. 2001

Bone Marrow Transplant

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Summary:Antithymocyte globulin (ATG) is accepted as a treatment option for steroid-refractory acute graft-versushost disease (GVHD). We conducted an international survey to determine how steroid refractoriness is defined and how ATG is used in clinical practice. Responses were received from 153 centers in 36 countries. The most common threshold steroid dose to define steroid refractoriness was 2 mg/kg/day (67% of respondents), and the median duration of treatment before failure was declared varied from 3 to 5.5 days, depending on whether failure was defined as 'progressed', 'not improved' or 'not resolved'. The threshold corticosteroid dose was significantly higher in pediatric centers than in adult or combined programs (P = 0.003). ATG was used routinely for treatment of steroid-refractory GVHD by 67% of the respondents. Horse ATG was used more frequently than rabbit ATG overall (50% vs 24%, P Ͻ 0.001), and predominance of horse ATG was most evident in the western hemisphere, in small-to medium-sized centers, and in pediatric centers. A wide variety of dose schedules for both drugs was reported. We conclude that there is some degree of variation in the definition of steroid refractoriness, especially between pediatric and nonpediatric programs, and no consensus has emerged in identifying the optimal ATG dose schedule in this setting. Bone Marrow Transplantation (2001) 28, 945-950. Keywords: graft-versus-host disease; treatment; antithymocyte globulin; antilymphocyte globulin; steroid-refractory; pediatric Antithymocyte globulin (ATG) was first introduced as a therapy for acute GVHD in 1974.1 Several single-agent ATG dose schedules or combination regimens that include horse or rabbit ATG have been evaluated in this setting, [1][2][3][4][5][6][7][8][9][10] and the activity demonstrated by these regimens enabled acceptance of ATG as a standard treatment for steroidrefractory acute GVHD. In the evaluation of new immuno-

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Section: Discussionmentioning

confidence: 71%

Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey

Hsu

May

Carrum

et al. 2001

Bone Marrow Transplant

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“…[7][8][9] Clearance of total ATG (rabbit or horse IgG) and active ATG (IgG capable of Ag-specific binding to cells) is more rapid in kidney transplant patients developing anti-rabbit or anti-horse antibodies. [10][11][12] In the HSCT setting, only one study has reported a few cases in which anti-ATG antibodies appeared shortly after transplantation, without signifying a potential clinical effect. 13 Reports on the pharmacokinetics and pharmacodynamics of ATG/ALG in adult [14][15][16][17] and pediatric 18,19 allogeneic HSCT recipients revealed a high variability between individuals.…”

Section: Introductionmentioning

confidence: 99%

IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk of acute GVHD

Zijde

Bredius

Jansen-Hoogendijk

et al. 2011

Bone Marrow Transplant

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Anti-thymocyte globulin (ATG), raised in rabbits, is frequently used in allogeneic hematopoietic SCT (HSCT), to prevent graft rejection and acute GVHD. In solid organ transplant patients, antibodies to rabbit IgG result in an enhanced clearance of ATG. The occurrence of such antibodies in HSCT recipients and their clinical impact is unknown. Concentrations of ATG and anti-ATG antibodies were measured in 72 pediatric HSCT recipients treated with ATG as part of the conditioning. Anti-ATG antibodies were detected in 20 children (28%), all transplanted with a non-depleted graft. IgG anti-ATG, alone or combined with IgM and/or IgA anti-ATG, appeared in 10 children. Four patients developed IgG anti-ATG antibodies early (before day 22) post-HSCT. They had steep drops in ATG levels and showed rapid T-cell recovery, which was associated with a significantly increased risk of acute GVHD. In six patients IgG anti-ATG responses occurred later (range 28-46 days) after HSCT without an increased risk of GVHD. A total of 10 children only mounted an IgM (and IgA) anti-ATG response, which was without major impact on ATG levels. These results indicate that early development of IgG anti-ATG antibodies has a major impact on acute GVHD. Routine analysis ATG/anti-ATG Ab measurement should be considered.

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“…Regan et al investigated the rates of sensitization based on IgG levels and found that sensitizations levels in those who received thymoglobulin were similar to those who received ATGAM; however, ATGAM sensitization lasted longer than thymoglobulin when patients were compared at 90 days [15]. Despite the patient's history of serum sickness, she tolerated ATGAM well.…”

Section: Discussionmentioning

confidence: 99%

Equine Anti-Thymocyte Globulin (ATGAM) administration in patient with previous rabbit Anti-Thymocyte Globulin (Thymoglobulin) induced serum sickness: A case report

Pryor¹,

Olyaei²,

Lockridge³

et al. 2017

J Clini Nephrol

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Thymoglobulin is a rabbit-derived anti-thymocyte antibody directed at T-cells and commonly used for induction immunosuppression therapy in solid organ transplantation, especially in immunologically high risk kidney transplant recipients. Despite its frequent use and effi cacy, the heterologous makeup of thymoglobulin can induce the immune system resulting in serum sickness which typically presents with rash, fever, fatigue, and poly-arthralgia in the weeks following drug exposure. ATGAM is another anti-thymocyte antibody, targeting the same epitopes, but differs from thymoglobulin by the animal in which the preparations are generated (equine vs. rabbit). Herein, we present a case of a patient with a known history of thymoglobulin-induced serum sickness, who presented with evidence of acute cellular and vascular rejection at their 12-month post-operative visit. Given their immunologically high risk status, they were successfully treated with ATGAM with improvement in their rejection and kidney function. To the author's knowledge, this is the fi rst case report of successful administration of ATGAM in a patient with a documented history of thymoglobulin induced serum sickness, demonstrating a possible treatment option for acute rejection in patients with reactions to thymoglobulin.

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Sensitization following Thymoglobulin and Atgam rejection therapy as determined with a rapid enzyme-linked immunosorbent assay

Cited by 18 publications

References 9 publications

Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey

Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey

IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk of acute GVHD

Equine Anti-Thymocyte Globulin (ATGAM) administration in patient with previous rabbit Anti-Thymocyte Globulin (Thymoglobulin) induced serum sickness: A case report

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