The Impact of Alemtuzumab Scheduling on Graft Versus Host Disease Following Unrelated Donor Fludarabine and Melphalan Allografts

Alemtuzumab conditioning is highly effective at reducing the incidence of acute and chronic graft versus host disease (GVHD) in reduced intensity fludarabine and melphalan transplantation with ciclosporin monotherapy. Less frequent and lower dose scheduling may be used with sibling donors but an optimal regimen for matched unrelated donors has not been defined. In this retrospective observational study of 313 patients, the incidence and severity of GVHD was compared in patients receiving three different dose schedules: the standard 100mg regimen (20mg on day -7 to -3), 60mg (30mg day -4 and -2) or 50mg (10mg on day -7 to -3). Patients treated with 100mg, 60mg or 50mg developed acute GVHD grade I-IV with an incidence of 74%, 65% and 64%, respectively, while 36%, 32% and 41% developed chronic GHVD. An excess of severe acute grade III/IV GVHD was observed in the 50mg cohort (15% vs. 2-6%; p = 0.016). The relative risk of severe acute grade GVHD remained more than three-fold higher in the 50mg cohort, compared with 100mg, after adjustment for differences in HLA match, age, gender mismatch, CMV risk and diagnosis (p = 0.030). The findings indicate that the 60mg alemtuzumab schedule was comparable to 100mg but more attenuated schedules may increase the risk of severe grade GVHD.