Association between pretransplant Thymoglobulin and reduced non-relapse mortality rate after marrow transplantation from unrelated donors.

A matched cohort study was designed to test the efficacy of polyclonal rabbit antiserum specific for human T cells (Thymoglobulin), administered in vivo on days 1-5 (2 mg/kg/day) before T cell-replete unrelated donor marrow transplantation. Thymoglobulin was given to 52 leukemic patients at Huddinge Hospital. Control patients matched for diagnosis, disease stage, age and treated with a similar regimen, apart from the omission of Thymoglobulin, were selected in Seattle during the same period (n = 104). All received conditioning with cyclophosphamide and TBI. In the study group all patients received 10 Gy single dose TBI, while the controls were given 12-14.4 Gy fractionated TBI. GVHD prophylaxis was cyclosporine and methotrexate. Patients were treated for grade I acute GVHD in the study group, and for grade II GVHD in the control group. Multivariable analyses were adjusted for patient and donor age and CMV serology, HLA matching, donor gender and marrow cell dose. Non-relapse mortality was lower in the study patients (hazard ratio = 0.30, 95% CI 0.12-0.75, P value = 0.005). The 5-year cumulative incidence of non-relapse mortality was 19% in the study cohort, and 35% in the control cohort. Overall mortality was also lower in study patients (hazard ratio 0.51, 95% CI 0.27-0.97, P value = 0.03). No significant difference in the risk of relapse was seen (P = 0.63). This suggests that Thymoglobulin during conditioning may reduce non-relapse mortality after unrelated donor marrow transplantation.