Chronic graft-versus-host disease (GVHD) is the most important long-term complication of bone marrow transplantation. It affects 40–60% of recipients, causes severe morbidity, decreases quality of life and increases the risk of mortality. Furthermore, the morbidity of chronic GVHD is long lasting; one-third of patients still takes immunosuppressive therapy about 5-6 years after the onset of chronic GVHD.
In a randomised, open-label, multicentre, phase 3 trial, 203 patients received either 4.5 mg/kg anti-thymocyte globulin (n=101) or no additional treatment (n=102) along standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate). Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma) and were between 16 and 70 years of age. They were matched to an unrelated donor who was a complete match or one locus mismatch at HLA-A, HLA-B, HLA-C, or DRB1 loci.
The primary endpoint was defined by freedom from immunosuppressive therapy without resumption at 12 months. Seven patients did not receive a transplant and were excluded.
Out of the 99 evaluated patients receiving anti-thymocyte globulin in addition to standard GCHD prophylaxis, 38 patients (38%) were free from immunosuppressive medication after a period of 12 months. This number was much higher than the 18 (19%) of 97 patients in the standard prophylaxis group ( [OR] 3.49 [95% CI: 1.60–7.60]; p=0.0016). The overall survival after 24 months was 70.6% (95% CI: 60.6-78.6) in the anti-thymocyte globulin plus prophylaxis group compared to 53.3% (42.8–62.8) in the standard GVHD prophylaxis group (HR 0.56, 95% CI [0.35–0.90]; p=0.017).
These results suggest a beneficial role of anti-thymocyte globulin addition to the standard treatment, resulting in less immunosuppressive medication and increased overall survival. The authors recommend using anti-thymocyte globulin prior to the standard treatment in patients undergoing unrelated donor transplantation.