UNASSIGNED: Reduced intensity conditioning with alemtuzumab, @entity3118 , and @entity3601 is an effective approach for the transplantation of @entity1 with @entity5 . Mixed chimerism and acute GVHD remain limitations on success. We hypothesized that higher levels of alemtuzumab at Day 0 would result in a low risk of acute GVHD, a higher risk of mixed chimerism, and delay early lymphocyte recovery, and that alemtuzumab level thresholds for increased risks of these outcomes would be definable. We collected data from 105 @entity1 to examine the influence of peri-transplant alemtuzumab levels (Day 0 +/- 72 hours) at the time of graft infusion on acute GVHD, mixed chimerism, and lymphocyte recovery. The cumulative incidences of initial grades I-IV, II-IV, and III-IV acute GVHD in @entity1 with alemtuzumab levels <=0.15ug/mL versus >=0.16ug/mL were 68% versus 18% (p<0.0001), 47% versus 13% (p=0.0002), and 32% versus 8%, respectively (p=0.005). The cumulative incidence of mixed chimerism in @entity1 with an alemtuzumab level of <=0.15ug/mL was 21%, versus 42% in @entity1 with levels of 0.16-4.35ug/mL, and 100% in @entity1 with levels >4.35ug/mL (p=0.003). @entity1 with alemtuzumab levels of <=0.15ug/mL or 0.16-0.56ug/mL had higher lymphocyte counts at Day +30 and higher T cell counts at Day +100 compared to @entity1 with levels of >=0.57ug/mL (all p<0.05). We conclude that peri-transplant alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following reduced intensity conditioning with alemtuzumab, @entity3118 , and melphalan. Future trials of targeted alemtuzumab dosing are warranted. We recommend an optimal targeted Day 0 therapeutic alemtuzumab range of 0.2-0.4ug/mL.

Alemtuzumab levels impact acute GVHD, mixed chimerism, _ lymphocyte recovery following alemtuzumab, XXXX _ melphalan RIC HCT.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity3118 :: ('MESH:C024352', 'Chemical') :: ['fludarabine'] @entity5 :: ('MESH:D009369', 'Disease') :: ['non-malignant disorders'] @entity3601 :: ('MESH:D008558', 'Chemical') :: ['melphalan']
@entity3118 :: (MESH:C024352,Chemical) :: ['fludarabine']
