Antithymocyte immunoglobulin (rabbit) 100mg/5ml solution for infusion vials

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 licence: CC BY-NC-ND

Haploidentical-related donor (HID) hematopoietic stem cell transplantation (HSCT) has undergone significant advances in recent decades. Granulocyte colony-stimulating factor- and antithymocyte globulin-based protocols and post-transplantation cyclophosphamide-based regimens represent two of the current T-cell-replete protocols in HID HSCT. Recently, the optimization of several critical transplant techniques has further improved hematopoietic reconstitution, decreased the incidence of relapse and graft-versus-host disease after HID HSCT, and extended the application of HID HSCT to older patients and those with non-malignant hematologic disorders. Combining this approach with novel immunotherapy could further improve the efficacy and safety of HID HSCT. This review focuses on recent progress in the optimization of HID HSCT.

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BACKGROUND: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti- N -glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. METHODS: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. RESULTS: CD3 + T cell depletion <100/mm 3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. CONCLUSIONS: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.

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ABSTRACT Background Acyclovir treatment is an efficient prophylaxis to prevent varicella‐zoster virus (VZV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Aims This single center retrospective study tried to determine if the lymphocytes immunophenotyping could help to determine the duration of prophylaxis, and evaluated complications, and associated risk factors for VZV infection. Methods and Results Eighty‐four children underwent an allogeneic HSCT, in which 77 received an acyclovir prophylaxis. Twenty‐one of the 77 had a VZV infection with an incidence rate of 1.30 per 100 patients‐months (exact 95% CI, 0.81 to 2.01). Among these 21 patients with VZV infection, 16 had an infection after withdrawing acyclovir prophylaxis within a median of 49 days (range, 11 days–5.8 months). Thirty‐five percent of the VZV infected patients were hospitalized, 9% had a visceral dissemination, and 9% had postherpetic neuralgia. In multivariate analysis, higher VZV infection rate was associated with conditioning regimen with total body irradiation, immunoglobulin substitution, and antithymocyte globulin. The incidence of VZV infection increased significantly when patients had a CD4+ lymphocytes count below 23% (cHR 3.28 [95% CI, 1.09–9.81]; p = 0.03) or a CD4 + /CD8 + ratio less than 0.9 (cHR 3.13 [95% CI, 1.04–9.36]; p = 0.04) at the time of stopping acyclovir prophylaxis. Conclusion After cessation of acyclovir prophylaxis, VZV reactivation can occur and be responsible for morbidity after allogeneic HSCT. This study suggests that the proportion of CD4+ lymphocytes and the CD4 + /CD8 + ratio can inform decisions about the duration of acyclovir prophylaxis after allogeneic HSCT to prevent VZV reactivation.

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BACKGROUND: Noninfectious, inflammatory myocarditis is a rare but serious side effect of immune checkpoint inhibitor (ICI) therapy. In severe cases, mortality rates are high and prompt multidisciplinary management, often including intensive care unit admission. CASE SUMMARY: This is a report focusing on a 54-year-old-man diagnosed with ICI myocarditis that highlights a treatment regimen which prolonged life in a fulminant steroid-refractory case. DISCUSSION: By combining immunosuppressive drugs from multiple therapeutic classes (antithymoglobulin and mycophenolate), cardiac inflammation was mitigated, with significant improvement in clinical condition. Debilitating symptoms resolved, and the patient was able to be weaned from inotropic agents. TAKE-HOME MESSAGE: Rabbit thymocyte antiglobulin and mycophenolate are useful rescue therapies in severe cases of steroid-refractory ICI myocarditis.

Abstract licence: CC BY-NC-ND

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) ( n = 36) with repeated immunosuppressive therapy (IST) ( n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG ( n = 16) or high-dose cyclophosphamide ( n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor ( n = 6), matched unrelated donor ( n = 7), or haploidentical donor ( n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II–IV and III–IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p &amp;lt; 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

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