Anti-thymocyte globulin (ATG)- or alemtuzumab-based graft-versus-host disease prophylaxis in reduced-intensity conditioning allogeneic hematopoietic cell transplantation (HCT) for patients 40 years and older with acute lymphoblastic leukemia in first complete remission: a study from the EBMT Acute Leukemia Working Party

For patients with high-risk acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (HCT) remains standard of care. In the setting of an HLA-matched unrelated donor HCT, in vivo T-cell depletion (TCD) for prophylaxis of graft versus host disease (GVHD) relies on anti-thymocyte globulin (ATG) in Europe and alemtuzumab in the UK. In a retrospective study from the EBMT registry, we pair-matched 90 ALL patients aged ≥40 years transplanted in CR1 according to age (median 56 years) and ALL subtype (37.8% Ph-negative B-ALL, 46.7% Ph-positive B-ALL, 15.6% T-ALL). Reduced-intensity conditioning included fludarabine/melphalan (94.4%) in the alemtuzumab and fludarabine/busulfan (36.7%), fludarabine/total body irradiation (21.1%), fludarabine/melphalan (14.4%) and thiotepa/busulfan/fludarabine (13.3%) in the ATG group. Two-year leukemia-free and overall survival were similar between groups (Alemtuzumab: 56.4% vs ATG: 50.7%, HR 0.82, p = 0.34, and 62.7% vs 62.9%, HR 0.91, p = 0.67), as were cumulative incidence of relapse (23.7% vs 23.9%, HR 0.89, p = 0.69) and non-relapse mortality (19.9% vs 25.4%, HR 0.75, p = 0.32), resulting in similar GVHD- and relapse-free survival (GRFS) of 48.9% vs 42.1%, HR 0.8, p = 0.24. With GVHD and infections as main reasons for death in both groups, we conclude that both IS strategies are both safe for RIC HCT of these ALL patients.