Authors' objectives:

The purpose of this report is to assess the usefulness of antilymphocyte immunoglobulins in the management of transplant rejection and aplastic anemia.

Authors' results and conclusions: For this report one meta-analysis, 10 narrative revisions, 27 randomized clinical trials, one cohort study and one case-controlled study were included. In addition, documents published on the subject issued by the US Food and Drugs Administration (FDA) and the Argentine Society on Hematology and a document on health coverage policies were also chosen. In kidney transplant, it is used for the management of acute rejection and as prophylaxis of chronic rejection. An increase in graft survival in acute rejection has been demonstrated. In several studies, its use has shown higher rates of rejection reversal and lower rates of recurrence for both indications, although an increase in patient's overall survival with the prophylactic use compared with schemes not containing ATG has not been demonstrated. In moderate to severe aplastic anemia it is used in patients that are not eligible for bone marrow transplantation (BMT), together with additional immunosuppressant therapy (cyclosporine and corticosteroids). Several RCTs and observational studies consistently show the superiority of this scheme, which leads to greater increases of peripheral blood counts and a decrease of transfusion needs, when compared with treatments that do not include globulins. In a cohort of 122 patients, the use of antilymphocyte immunoglobulins (ATG) and cyclosporine for severe aplastic anemia showed that the response rate was 60% at 3 months after initial treatment, 61% at 6 months and 58% at one year. Overall survival at 7 years was 55%. One RCT published the results at 4 months from 84 patients, mostly with severe aplastic anemia. Approximately two thirds responded to ATG, Cyclosporine A and a short course of methylprednisolone. The combination was significantly more effective than ATG and methylprednisolone alone (response rate, 70% vs 41%; P=0.015). In bone marrow transplant, it is used in the prevention of graft versus host disease (GvHD) and for acute GvHD management. There are few RCTs, but the arms that include ATG show reduction in acute or chronic disease. All the studies show an improvement in the incidence of acute GvHD grades II and III-IV. The populations had little follow-up and relatively few patients. These publications agree with retrospective analysis which included greater numbers of patients. However, to date it is not possible to assert that the use of ATG would reduce transplant-related mortality, at least at short-term. In transplant of other organs such as liver, heart, lung and pancreas, there are many RCTs also showing lower rejection rates, especially at short-term. Adverse effects: The formulations may contain antibodies against blood components which induce leucopenia, thrombocytopenia or hemolysis. This can be more frequent in patients with aplastic anemia. Adverse effects are generally transient and dose-dependant. Other effects observed are lymphoproliferative disorders associated with Epstein-Barr virus, including viral reactivation and prolonged immunodeficiency.

Authors' recommendations: Most evidence comes from randomized clinical trials, most present methodological problems such as short follow-ups with patient loss, and heterogeneous populations (level of evidence 1b). There are factors that make evidence assessment even more difficult: the individual and batch variability among globulins, scarce number of patients enrolled in many of the studies and low doses used in previous studies. The use of globulins is well supported by evidence for aplastic anemia, bone marrow transplant and graft versus host disease prevention, and management of rejection in kidney transplant patients (acute and chronic rejection prophylaxis). For other solid organ transplants there is less evidence.

Authors' methods: Overview

Project Status: Completed

URL for project: http://www.iecs.org.ar/

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Argentina

Organisation Name: Institute for Clinical Effectiveness and Health Policy

Contact Address: Dr. Emilio Ravignani 2024, Buenos Aires - Argentina, C1414 CABA

Contact Name: info@iecs.org.ar

Contact Email: info@iecs.org.ar

Copyright: Institute for Clinical Effectiveness and Health Policy (IECS)