Alemtuzumab markedly reduces chronic GVHD without affecting overall survival in reduced-intensity conditioning sibling allo-SCT for adults with AML

Abstract

By retrospective analysis of 88 patients from the British Society of Blood and Marrow Transplantation registry, we investigated the effect of in vivo T-cell depletion in HLA-identical sibling reduced-intensity conditioning (RIC) allografts for adult AML by comparing patients who received alemtuzumab with those without alemtuzumab conditioning. Both groups were equivalent for age, sex, karyotype and disease status at transplant. With a median follow-up of 27 months (3-72 months) and 48 months (7-72 months), the 2-and 5-year overall survival, with or without alemtuzumab, is 60 and 60% (P ¼ 0.80) and 61 and 53%, respectively (P ¼ 0.85). The 2-year nonrelapse mortality is 12% with alemtuzumab, and 17% without alemtuzumab (P ¼ 0.49). The 2-year relapse rate is 35% with alemtuzumab compared with 19% without alemtuzumab (P ¼ 0.28). Grades II-IV acute GVHD occurred in 22% (8/37) without alemtuzumab compared with 14% (7/51) given alemtuzumab (P ¼ 0.25). Extensive chronic GVHD occurred in 47% (14/30) not given alemtuzumab compared with 4% (2/45) who were given alemtuzumab (P ¼ 0.001). Among evaluable patients, the risk of infections was higher in those treated with alemtuzumab compared with those not treated with alemtuzumab (79 vs 57%, respectively, P ¼ 0.02). In conclusion, alemtuzumab has a beneficial effect by reducing chronic GVHD without affecting overall survival. Further studies are warranted before alemtuzumab can be recommended as standard in RIC allografts for AML.

Impact of immune modulation with anti–T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies

“…20 Malladi et al also observed higher infection risks and lower chronic GVHD in 51 patients who received alemtuzumab compared with 37 patients who did not. 21 We were unable to explore differences in cytomegalovirus reactivation between patients who received alemtuzumab and T cellreplete transplantations in the current analysis, but cytomegalovirus reactivation was not a more frequent cause of death in the alemtuzumab group. Unlike the current analysis, neither prior report observed differences in relapse.…”

Alemtuzumab for the prevention and treatment of graft-versus-host disease

“…The use of alemtuzumab as a conditioning regimen was shown to be associated with reduced incidence of extensive chronic GVHD in the analysis of 88 patients receiving transplantation from an HLA-identical sibling graft [43]. However, the effect of alemtuzumab on the treatment of refractory chronic GVHD was reported only as a case report.…”

Methotrexate dose delivery is more important than ciclosporin level in graft-versus-host disease prophylaxis following T-replete reduced-intensity sibling allogeneic stem cell transplant

“…One of the major areas of debate is the role of T cell depletion. T cell depletion in RIC HSCT has been shown to reduce the incidence of acute and chronic graft-versus-host disease (a/cGvHD) [2][3][4][5] but is associated with poorer disease control due to impairment of the graft-versus-leukaemia (GvL) effect [6]. The net outcome appears to be that overall survival is comparable between T-replete and T-depleted HSCT, with higher relapse-related deaths in T-depleted HSCT and higher transplant related mortality, including deaths from GvHD and its treatment, in T-replete HSCT [4,5].…”