Equivalent Outcome Between Older Siblings and Unrelated Donors After Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients Older Than 50 Years with Acute Myeloid Leukemia in First Complete Remission: A Report From the ALWP of EBMT

Current data indicates that allogeneic hematopoietic stem cell transplantation (HSCT) provides identical long-term survival for patients (pts) with acute myeloid leukemia (AML) receiving grafts from matched 8/8 unrelated donor (MUD) or matched sibling donor (MSD) after reduced intensity conditioning (RIC) regimen. Given those results, one may question the requirement for an “older” MSD when a healthy younger MUD is available. This study assessed the impact of older age of MSD on outcomes post-HSCT for pts older than 50 years with AML in first complete remission (CR1) transplanted after a RIC regimen.

From January 2000 to December 2010, this retrospective multi-center study included 1102 pts with AML in CR1 who received PBSC after a RIC regimen, either from MSD (n=854) or from 8/8 HLA MUD (n=248). Conditioning regimen was fludarabine-based in 95% of the pts and Graft versus Host Disease (GvHD) prophylaxis consisted of cyclosporine plus MMF in 42% of cases. To address the role of donor age in our population, 3 groups of pts were defined: pts who were transplanted from a MUD (“MUD group”), pts who received their graft from a sibling aged less than 60 years old (“MSD<60 group”) and pts who were transplanted from a sibling aged of 60 years old or more (“MSD³60 group”).

Patient characteristics were similar between the 3 groups for gender, disease distribution (FAB classification) and cytogenetic risks (MRC classification). Recipients were younger in the MSD<60 group (57 years versus 60 and 61 years for MUD and MSD³60, respectively, p<0.001). Donors were younger for MUD (median age 35 years versus 53 years and 64 years for MSD<60 and MSD³60 respectively, p<0.001). In the MUD group, pts were transplanted more recently (2009 versus 2006 and 2007 for MSD<60 and MSD³60 respectively, p<0.001), with a longer time interval between diagnosis and HSCT (184 days versus 154 days and 151 days for MSD<60 and MSD³60 respectively, p<0.001) and the conditioning regimen included more ATG (p< 0.0001). The median follow-up was 24 months (range, 2–122) for MUD, 42 months (range, 1.5–140) for MSD<60 and 33 months (range, 1–129) for MSD³60. During evolution, the cumulative incidence (CI) of acute GvHD was 28% in MUD versus 20% and 17% in MSD<60 and MSD³60, respectively (p=0.006) while the CI of chronic GvHD at 2 years was about 50% in each group (p=0.93). CI of treatment related mortality (TRM) and relapse as well as leukemia free survival (LFS) and overall survival (OS) were not different at 2 years between the 3 groups (Table 1). In multivariate analysis, TRM was decreased in pts who received ATG in the conditioning regimen (HR: 0.62; 95%CI 0.41–0.95; p=0.03). A longer interval between AML diagnosis and CR1 (>median) was the only factor associated with relapse (Hazard ratio - HR: 1.35; 95%CI 1.05–1.74; p=0.02). Two independent factors were associated with worse LFS: a longer delay between AML diagnosis and CR1 (HR: 1.34; 95%CI 1.09–1.64; p=0.01) and CMV donor seropositivity (HR: 1.28; 95%CI 1.02–1.6; p=0.04). For pts alive after 2 years post HSCT (n=454), a significant higher rate of TRM was found in pts transplanted from MUD compared with the 2 other groups (Landmark analysis, Table 2).

These data suggest equivalence of outcome using MUD, MSD<60 or MSD³60 in pts older than 50 years with AML in CR1 transplanted after a RIC regimen. Until prospective studies are completed, this study supports the recommendation to consider HLA-identical donors for HSCT even after 60 years of age (if eligible for donation) prior to younger 8/8 MUD for pts with AML older than 50 years in CR1 after a RIC regimen.

No relevant conflicts of interest to declare.