The impact of the intensity of
graft-versus-host-disease immunoprophylaxis on
transplantation outcomes in patients undergoing
transplantation following reduced-intensity conditioning is unclear. This study addresses this issue in 228 adult patients above 50 years of age with
acute myeloid leukemia in first complete remission given peripheral blood stem cells from HLA-identical siblings after
fludarabine and 2 days of intravenous
busulfan reduced-intensity conditioning. A total of 152 patients received
anti-thymocyte globulin, either in combination with
cyclosporine A in 86 patients (group 1), or with
cyclosporine A and
mycophenolate mofetil or short course
methotrexate in 66 patients (group 2). The remaining 76 patients did not receive
anti-thymocyte globulin but were given
cyclosporine A and
methotrexate or
mycophenolate mofetil (group 3). Incidences of grade II-IV acute
graft-versus-host-disease were comparable in the three groups (16.5%, 29.5% and 19.5% in groups 1, 2 and 3, respectively, P=0.15). In multivariate analysis, the absence of
anti-thymocyte globulin was the only factor associated with a higher risk of
chronic graft-versus-host-disease (P=0.005), while the use of triple immunosuppression (group 3) was associated with an increased risk of relapse (P=0.003). In comparison to
anti-thymocyte globulin and
cyclosporine A alone, the other two strategies of
graft-versus-host-disease prophylaxis were associated with reduced
leukemia-free survival and overall survival (P=0.001 for each parameter), independently of the dose of
anti-thymocyte globulin. These data suggest that fine tuning of the intensity of this prophylaxis can affect the outcome of
transplantation and that
anti-thymocyte globulin and
cyclosporine A alone should be the preferred combination with the
fludarabine-
busulfan reduced-intensity conditioning regimen and sibling donors.