Similar Outcome Between Siblings, Unrelated Donors and Cord Blood After Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients Older Than 50 Years with Acute Myeloid Leukemia in Complete Remission
Authors: de Latour Regis Peffault , Brunstein Claudio G , Porcher Raphael , Chevallier Patrice , Robin Marie , Warlick Erica D. , Xhaard Alienor , Ustun Celalettin , Dhedin Nathalie , Mohty Mohamad , Socie Gerard , Weisdorf Daniel J. 
Published: October 2019

Abstract
Abstract 1985

Introduction:
For older patients with acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (HCT) provides the best chance of long-term survival. Because older patients less often have available healthy sibling donors, alternative donors may be more important. We compared the outcomes of reduced intensity conditioning (RIC) HCT for AML patients over 50 years in complete remission (CR) using matched sibling (SIB), unrelated (URD) or umbilical cord blood (UCB) donors.

Patients, methods and HCT characteristics:
From January 2000 to December 2010, 197 consecutive patients (median age 59, range 50–74) received RIC and allogeneic HCT in 3 independent centers, either from SIB (n=82), HLA 8/8 allele-matched URD (n=35) or UCB (n=80; 10 single unit). One patient received an HLA 7/8 allele-mismatched URD. SIB and URD all received peripheral blood as source of stem cells. Conditioning was fludarabine-based in the majority (86%) and most received Graft versus Host Disease (GvHD) prophylaxis using cyclosporine plus MMF (79%). 68% were in CR1; 6% of patients had good risk cytogenetics and 29% had poor risk (MRC classification).

Results:
Patient characteristics were similar between the 3 groups for age, gender, CR# and the median time interval from diagnosis to HCT. UCB recipients had more frequent high risk features including: KPS<90% (19% versus 10% and 3% for SIB and URD, respectively, p=0.04); female donor: male recipient (44% versus 20% SIB and 17% URD, p=0.04); and somewhat more high risk cytogenetics (UCB 34%, SIB 22%, URD 17%, p=0.06). Conditioning regimens using Fludarabine and low dose TBI were more frequent in UCB: 100% vs. 24% for SIB and 11% for URD, p<0.0001); Fludarabine and Busulfan (more in URD: 71% vs. 43% for SIB and 0 for UCB, p<0.0001); and Cyclophosphamide plus low dose TBI (more in SIB: 28% vs. 3% for URD and 0 for UCB, p<0.0001) also differed between the 3 groups. Moreover, more ATG was used in URD (86% vs. 29% for SIB and 29% for UCB, p<0.0001). After a median follow-up of 39 months (range 2 to 104, 42 months for SIB, 25 months for URD and 51 months for UCB), 103 patients survive. The 3-year cumulative incidence function (CIf) of transplant related (non-relapse) mortality (TRM) was 18%, 14% and 24% with SIB, URD and UCB, respectively (p=0.22). The 3-year CIf of relapse was 33%, 29% and 43% with SIB, URD and UCB, respectively (p=0.04). Consequently, the 3-year CIf of leukemia free survival (LFS) was 48%, 57% and 33% with SIB, URD and UCB, respectively (p=0.009). In multivariate analysis, poor cytogenetic risk was associated with a higher rate of relapse (HR 1.7 [95% CI 1.0–3.0], p=0.04), worse LFS (HR 1.6 [1.0–2.5], p=0.03) and a trend for worse OS (HR 1.6 [1.0–2.4], p=0.06), but survival using each donor sources was similar (UCB HR 1.2 [0.7–2.1], p=0.45; URD 1.2 [0.5–2.7], p=0.73 as compared to SIB). Adjusted, 3-year OS was 55% with SIB, 45% with URD and 43% with UCB (p=0.26) (Figure 1). The use of TBI-containing regimen was associated with a non-significant, but worse OS in recipients of MRD and URD grafts (HR 1.8 [0.9–3.8], p=0.11). Outcome was similar between the 3 centers.

Conclusion:
These data suggest equivalence of outcome using SIB, URD or UCB in patients >50 years with AML in CR. Poor cytogenetic risk was the dominant prognostic factor, influencing relapse and LFS with a trend for worse OS. Until prospective studies are completed, this study supports the recommendation to consider SIB, URD or UCB for HCT for patients with older AML in CR.

Disclosures:
No relevant conflicts of interest to declare.