Abstract
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is recommended for patients with high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Whereas conventional myeloablative conditioning is associated with a considerable treatment-related mortality (TRM), less intensive conditioning regimens may not be as efficient for long-term disease control, particularly in high-risk patients. Here, we present a retrospective single-institution analysis of 90 patients with median age of 39 years (range 17–66) with high-risk AML, i.e. based on non-favorable karyotype (not t(15;17), t(8;21) or inv(16)), blast persistence on day 16, the failure to achieve CR1 after two courses of induction therapy or the presence of secondary or therapy-induced AML, who underwent alloHSCT in CR1 between 1994 and 2007 (median follow-up 26, range 1–147 months). As stem cell source bone marrow (BM) was used in 17/90 patients (19%), whereas 73/90 patients (81%) received peripheral blood stem cells (PBSC). In 61/90 patients (68%) standard high-dose myeoloablative conditioning (12 Gy TBI + 120 mg/kg CY), (TBI group), was administered, whereas 29/90 (32%) patients received reduced-intensity conditioning (FLUD/BU/ATG)(RIC). A matched-related donor (MRD) was available for 62/90 patients (69%), whereas alloHSCT was performed from an unrelated donor (URD) in 28/90 patients (31%). Prevention of graft-versus-host disease (GvHD) consisted of CSA/MTX in the TBI group or CSA/MMF in the RIC group. 48/90 (53%) patients had a normal karyotype, whereas 39/90 patients (43%) displayed an aberrant karyotype. Projected overall survival (OS) and disease-free survival (DFS) of the whole cohort at 1, 3, and 5 years was 74%, 62%, and 57% and 72%, 58%, 54%, respectively. Causes of death were relapse (17/90 = 19%) or TRM (17/90 = 19%). The OS in the TBI group versus the RIC group was 72% vs. 79% at 1 year, 64% vs. 52 at 3 years, and 59% vs. 52% at 5 years (p = 0.78). Furthermore, there was no significant difference in the 1, 3, and 5-years DFS rates (72%, 62%, 57% vs. 75%, 50%, 49%) between the two groups. OS and DSF reached a plateau beyond 39 months (TBI group) and 33 months (RIC group). Relapse and TRM in the TBI group versus the RIC group were 21% vs. 14% and 16% vs. 24%. A comparison of the OS between the subgroups with a normal (n = 48) versus an aberrant (n = 39) karyotype revealed no significant difference at 1 year (83% vs. 65%), 3 years (70% vs. 47%), and 5 years (67% vs. 45%) (p = 0.06). Notably, there was no significant difference in the incidence of chronic graft-versus-host disease (cGvHD) between the TBI group and the RIC group (46% vs. 52%). Taken together, these results suggest that patients with AML in CR1 achieve a robust and durable long-term remission irrespective of the conditioning intensity (TBI vs. RIC) and the presence of an aberrant karyotype.
Anti‐thymocyte globulin for graft‐versus‐host disease prophylaxis in patients with intermediate‐ or high‐risk acute myeloid leukaemia undergoing reduced‐intensity conditioning allogeneic stem cell transplantation in first complete remission – a survey on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation