Impact of alemtuzumab versus anti-thymocyte globulin after unrelated allogeneic stem cell transplantation with reduced-intensity conditioning as treatment for AML in CR1: a survey from the Acute Leukaemia Working Party of the EBMT

In vivo T cell depletion of the graft with anti-thymocyte globulin (ATG) or with alemtuzumab has been frequently used in the setting of RIC allo-SCT from unrelated donors. This survey compared allo-SCT outcomes between 364 AML patients in first CR given unrelated PBSC after chemotherapy-based RIC and given either ATG (n=213) or alemtuzumab (n=151) in the conditioning regimen. Alemtuzumab patients were more frequently given grafts from HLA-mismatched donors (30% versus 16% having at least 1/10 HLA-mismatch with their donor, P=0.005), and were conditioned more often with melphalan-based RIC (62%), while ATG recipients were more frequently conditioned with busulfan-based RIC (84%). Median time to neutrophil engraftment (>500 ANC) was 16 days in ATG recipients, versus 12 days in alemtuzumab recipients (P<0.001). The incidence of grade II-IV acute GVHD was 28% in ATG recipients (9 patients with grade IV) and 24% (NS) in alemtuzumab recipients (2 patients with grade IV). Two-year incidences of chronic GVHD, relapse and NRM were 45%, 23% and 14%, respectively, in ATG recipients, and 47% (NS), 25% (NS) and 25% (P=0.008), respectively, in alemtuzumab recipients. Two-year OS and LFS were 69% and 63%, respectively, in ATG recipients, versus 55% (P=0.003) and 51% (P=0.02), respectively, in alemtuzumab recipients. Death from infection occurred in 7% of ATG recipients, versus 12% of alemtuzumab recipients. When the analysis was restricted to the 210 patients given grafts from 10/10 HLA-matched unrelated donors, the use of alemtuzumab (n=64) remained signifi cantly associated with higher NRM (22% vs 9%, P=0.007), lower LFS (58% vs 69%, P=0.07), and lower OS (62% vs 74%, P=0.04). In multivariate analyses (performed in patients given grafts from 10/10 HLA-matched donors), in comparison to the use of ATG, the use of alemtuzumab was associated with higher NRM (HR=2.5, P=0.025), a statistically non-signifi cant but higher relapse rate (HR=1.7, P=0.18), and signifi cantly worse LFS (HR=0.5, P=0.013) and OS (HR=0.4, P=0.002). In summary, this homogeneous cohort of AML patients transplanted in fi rst CR and given PBSC grafts from unrelated donors, the use of alemtuzumab in comparison with ATG was associated with worse LFS and OS.