Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning (RIC) Is Effective for Long-Term Disease Control in High-Risk AML Patients in First Complete Remission.
Authors: Hemmati Philipp G. , Massenkeil Gero , Terwey Theis H. , Neuburger Stefan , le Coutre Philipp , Vuong Lam , Dorken Bernd , Arnold Renate 
Published: October 2019

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.