Impairment of leukaemia-free survival by addition of interleukin-2-receptor antibody to standard graft-versus-host prophylaxis

Abstract

Graft-versus-host disease (GVHD) is the most important adverse effect of HLA-matched allogeneic bone-marrow transplantation. T-cell depletion of the graft eliminates GVHD but also causes an unacceptable increase in rejections and leukaemic relapses. We have attempted to block the activation of resting T cells with a monoclonal antibody against the interleukin-2 receptor (33B3.1). 101 patients with leukaemia (acute lymphocytic 22, acute myelogenous 34, chronic myeloid 45) in first complete remission or first chronic phase were randomly assigned to groups receiving standard post-transplantation immunosuppression (methotrexate plus cyclosporin; n = 50) or the standard treatment plus antibody 33B3.1 (n = 51). There were 2 graft failures in the 33B3.1 group. The antibody did not significantly affect the cumulative frequency of acute GVHD of grade 2 or worse (19 [38%] vs 23 [46%]) but merely delayed its onset (median 36 [IQR 21-70] vs 25 [11-44] days; p < 0.01). At median follow-up of 58 (range 41-71) months, the antibody-treated group had significantly lower leukaemia-free survival (p < 0.05) mainly because of a progressive increase in the rate of late relapses (p = 0.08). Our findings confirm the importance of T cells in transplantation for leukaemia. The fine balance between the early modulation of transplant immunity and leukaemic control suggests that further anti-leukaemic measures may be needed when attempts are made to improve tolerance between the graft and the leukaemic host.