Donor Choice for Allogeneic Stem Cell Transplantation for AML – A Retrospective Single Centre Long-Term Analysis,
Authors: Ayuk Francis , Bernhardt Friedericke , Zabelina Tatjana , Stübig Thomas , Alchalby Haefaa , Wolschke Christine , Lellek Heinrich , Bacher Ulrike , Zander Axel R. , Kröger Nicolaus 
Published: October 2019

Abstract
Abstract 4147

Introduction:
AML is one of the most common indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT). A matched sibling donor (matched related donor, MRD) is generally considered preferable to an unrelated donor (UD). It has been reported before that donor age may influence outcome of allo-HSCT. Sibling donors of older patients will generally be old as well. How a young unrelated donor compares with an old sibling donor is unclear. In this retrospective study we evaluate the influence of donor age on outcome of MRD and UD allo-HSCT and compare the impact of young unrelated donors vs. old related donors on overall survival (OS).

Patients and Methods:
We performed a retrospective analysis of 298 consecutive patients transplanted for AML at our center between January 2000 and December 2009. Median follow-up was 56 months. The median age of donors and patients were 39 and 50 yrs. respectively. These two ages were used as cut-off points for young and old donors and patients respectively. Accordingly, four donor aged groups were assigned: UD ' 39 years, UD > 39 yrs, MRD ≤ 39 yrs and MRD > 39 yrs. Analyses were performed in the more homogeneous population of patients in CR at time of transplant (n = 170) as well for patients older than 50 years and in CR at time of transplant (n = 77). Patient characteristics for the 170 Patients in CR are summarized in table 1.

Results:
In the cox-regression multivariate analysis of all 298 patients including factors significant in the univariate analysis (conditioning intensity, cytogenetic risk group, remission status at time of transplant and donor age) remission status (RR: 1.88, p < 0.001) and cytogenetic risk (RR: 5.50, p = 0.004) significantly impacted overall survival (OS). Donor age (p = 0.08) and patient age (p = 0.063) tended to influence OS in this group.
In the more homogenous group of 170 patients who were in CR at time of transplantation the Kaplan Meier estimated 5 yr OS was 66% (95% CI: 54%-78%) for patients transplanted from UD ≤ 39 yrs, 41% (95% CI: 25–57%) for UD >39 yrs, 61% (41–81%) for MRD ≤ 39 yrs and 33% (19–47%) for MRD > 39 yrs (p =0.002 comparing all 4 groups), fig. 1. OS of patients with UD ≤ 39yrs was significantly better than for those with MRD > 39 yrs (66% vs. 33%, p = 0.001). In the multivariate cox-regression analysis (including donor age, patient age and cytogenetic risk) only donor age (p = 0.001) and cytogenetic risk (p = 0.011) significantly impacted OS whereby MRD > 39 yrs. was associated with poorer OS compared to UD ≤ 39 yrs (RR: 3.07, p< 0.001). Further subgroup analyses of patients > 50 years old and in CR at time of transplant (n = 77) revealed similar findings with 5 yr OS of 62% for UD ≤ 39 yrs and 25% for MRD >39 yrs (p = 0.016).

Conclusions:
In patients undergoing allo-HSCT for AML our findings suggest that young unrelated donors may improve survival outcome as compared to old related donors. Further studies are necessary to confirm these findings and better define possible age limits for choosing young unrelated donors vs. older sibling donors.

Disclosures:
No relevant conflicts of interest to declare.