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Key Clinical Message: This report describes a rare case of developing Guillain–Barre syndrome (GBS) following receiving rabbit antithymocyte globulin (ATG) after kidney transplantation to prevent acute allograft rejection in a 34‐year‐old man. The patient presented severe pain in the right temporomandibular joint, fever, chills, myalgia, polyarthralgia, and bone pain. Twelve hours later, he developed quadriplegia, paresthesia, and a limited range of active motions in all extremities. No antecedent viral or bacterial infection was identified. The EMG/NCV evaluation displayed acute inflammatory sensory‐motor polyneuropathy. After the administration of GBS treatment, the neurologic symptoms started to improve. Over a few days, the reflexes came back completely, and the patient was able to walk. To our knowledge, this is the second case report of ATG‐related GBS after kidney transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Antihuman thymocyte immunoglobulin, used as an induction agent in renal transplantation, is of two types - thymoglobulin and grafalon (formerly ATG-Fresenius). In this study, we compared outcomes with these two agents. Methods: This was a single-center retrospective study of patients transplanted from January 2017 to October 2019, who received either grafalon or thymoglobulin induction. Grafalon or thymoglobulin was given at 6 and 3 mg/kg, respectively, followed by standard triple immunosuppression of tacrolimus, MMF, and prednisolone. Results: Median follow up was 22 (3-36) months. Thymoglobulin was given to 255 patients, whereas 78 patients received grafalon. Baseline demographics were similar between the two groups although significantly more patients in the grafalon group received ABO incompatible transplant (15% vs. 4.3%; P = 0.002). Patient survival was similar between the two groups (99% in grafalon vs. 98.8% in thymoglobulin; P = 1.0). Death censored graft survival was also similar (99% in grafalon vs. 100% in thymoglobulin; P = 0.23). Biopsy proven acute rejection (BPAR) was significantly higher in the grafalon group (12.8% vs. 5.1%, P = 0.04). The significance persisted after multivariable regression analysis (P = 0.02). Other outcomes such as infection rate and estimated glomerular filtration rate on last follow up were comparable between the two groups. Conclusions: Grafalon (6 mg/kg dose) when used as an induction agent was associated with significantly higher rate of BPARs as compared to thymoglobulin (3 mg/kg dose) although with comparable short-term patient and death censored graft survival, graft function, and infection rates. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CsA) is the first-line therapy for acquired aplastic anemia (AA) in those not suitable for bone marrow transplant. Horse ATG (hATG) is preferred for this purpose, but its use is often impeded by shortages and costs. Being a rare disease, there is limited data on this therapy. This study aimed to evaluate this therapy in a large cohort of AA patients from western India. We retrospectively analyzed AA patients who received an indigenous preparation of hATG along with CsA as first-line treatment, between 2012 and 2015, at our center and evaluated the response, survival, and occurrence of adverse events. The response was further assessed separately for adults and children. During the period, 91 AA patients (4 non-severe, 57 severe and 30 very severe) were treated with IST. At 2 years, 23.5% adults and 39.1% children showed complete response and an overall of 68.1% cases became transfusion independent. More than half of the patients developed febrile neutropenia while roughly one sixth of the patients developed gum hypertrophy and/or hypertension. Two patients had clonal evolution. Mortality rate was calculated to be 31%; most common causes of death were infection and intracranial hemorrhage. The results of the study substantiate the effectiveness of IST in AA, using an inexpensive indigenous preparation of hATG along with CsA. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • There is interindividual variability in the antilymphocyte globulin (ALG) effect, but there is no pharmacokinetic–pharmacodynamic study of this subject. • In addition, a time dependence of the pharmacokinetics of some therapeutic antibodies has been described. • ALGs may partly act by antibody-dependent cellular cytotoxicity (ADCC), but their mechanism of action in humans is not known. WHAT THIS STUDY ADDS • Horse ALG pharmacokinetics can be described using a two-compartment model with time-dependent central volume of distribution. • After an initial concentration-independent lymphocyte depletion, the concentration–effect relationship can be described using a physiological indirect response model. • The genetic polymorphism of FcγRIIIa at position 158 may influence the ALG concentration–effect relationship and these polyclonal antibodies may therefore act by ADCC. AIMS Polyclonal antilymphocyte globulins (ALGs) are currently used in transplantation, but the sources of interindividual variability of their effect are poorly understood. No pharmacokinetic–pharmacodynamic (PK–PD) study of ALG is available. Moreover, the genetic polymorphism of FcγRIIIa, a receptor for the Fc portion of immunoglobulins involved in antibody-dependent cellular cytotoxicity (ADCC), may influence their concentration–effect relationship. METHODS Fourteen kidney transplant patients treated by horse ALG were included in a prospective, noncomparative study. A population two-compartment PK model including a time dependence of the central volume of distribution was developed. Total lymphocyte count was used as biomarker of effect. Concentration–effect data were described using a physiological indirect response model, combining concentration-dependent and -independent inhibitions of lymphocyte input into the circulation. In addition, six kidney transplant patients in whom ALG concentrations were not available were included retrospectively. All patients were genotyped for FCGR3A. RESULTS Both the PK and the PK–PD model described the data satisfactorily and showed high interindividual variability. Asymptotic T1/2-α and T1/2-β-values were 1.3 and 25 days, respectively. The concentration of ALG leading to a 50% inhibition of lymphocyte input (IC50) was lower in FCGR3A-V carriers than in FCGR3A-F/F patients (383 ± 199 vs. 593 ± 209 mg l−1, P = 0.008). CONCLUSIONS This is the first description of the ALG effect on lymphocyte count using PK–PD modelling. Our results show that part of the variability in their concentration–effect relationship may be explained by FcγRIIIa genetic polymorphism and therefore that horse ALG may deplete lymphocytes by ADCC. [ABSTRACT FROM AUTHOR]

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C–positive (HCV-positive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCV-positive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P ≤ .01). ATG induction did not influence the risk of graft loss from HCV-related disease (P =.75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P =.39) or patient survival (P =.11) in HCV-positive recipients. [Copyright &y& Elsevier]

Provides information on the management of patients who receive antithymocyte globulin (ATG) for aplastic anemia (AA) and myelodysplastic syndrome. Description of ATG; Symptoms of AA; Treatment recommendations for AA.

Introduction: There are limited data to guide optimal treatment strategies for acute cellular rejection (ACR) based on Banff grade for pediatric kidney transplant recipients. This report reviews a large pediatric transplant center's experience with ACR. Materials and Methods: A retrospective analysis of pediatric kidney transplant recipients at our center from 2007 to 2014 was performed. Primary outcomes were incidence of graft failure and graft function one year following ACR based on Banff grade and treatment received. Results: A total of 204 patients were reviewed, of which 65 received rejection treatment with either an oral steroid cycle (n = 16), intravenous steroid pulse (n = 28), or anti‐thymocyte globulin (rATG, n = 21). Overall, patients received rATG for treatment of more severe rejection associated with impaired graft function and as a group experienced statistically significant improvements in eGFR over the year following treatment, though most did not regain baseline graft function. Discussion: Our data suggest that rATG is partially effective in treating ACR, but our study was underpowered to determine the effect of different treatments based on Banff grade. Since there is limited literature to guide clinical treatment of ACR in children, large transplant centers should collaborate to evaluate outcomes and establish evidence‐based practice. [ABSTRACT FROM AUTHOR]