Current Outcome Of HLA Identical Sibling Vs Unrelated DONOR Transplants In Severe Aplastic Anemia : An EBMT Analysis

Unrelated donor (UD) transplants for patients with acquired severe aplastic anemia (SAA) have been known to yield inferior results when compared to transplants from HLA identical siblings (SIB). With the significant improvement of UD transplants over the past decade, on may ask whether this is still true.

To compare the outcome of UD with SIB transplants in recent cohort of patients reported to the European Group for Blood and Marrow Transplantation (EBMT) Aplastic Anemia Registry.

We have analyzed 1500 patients with acquired aplastic anemia (SAA), who received a first bone marrow (BM) or peripheral blood (PB),. HLA matched transplant between 2005 and 2009, from identical siblings (n=975) or unrelated donors (n=525). Excluded were cord blood grafts. Clinical characteristics of the two groups were different: although SIB vs UD grafts had comparable age (20 vs 21 years median age , p=0.1), SIB grafts were performed earlier (152 vs 607 median days from diagnosis, p<0.00001), had less frequently anti-thymocyte globulin (ATG) in the conditioning regimen (50% vs 61%, p<0.0001), had less frequently radiation based conditioning (5% vs 31%, p<0.00001), and more frequently received marrow as a stem cell source (61% vs 53%, p=0.002).

The cumulative incidence (CI) of engraftment was 91% for both SIB and UD transplants; and the CI of acute GvHD grade II-IV was11% in SIB and 25% in UD grafts (p<0.0001). Infection was the leading cause of death (10% UD, 8% SIB), followed by GvHD (6% UD vs 3% SIB) and rejection (1,7% and 1,4% respectively).

In multivariate COX analysis the strongest negative predictors of survival was the use of PB as a stem cell source (RR 2, p<0.00001), followed by patient age >20 years (RR 2.0, p<0.0001), an interval diagnosis-transplant (Dx-Tx) >180 days (RR 1.3, p=0.006) and no anti-thymocyte globulin (ATG) in the conditioning (RR 1.6, p=0.002). The use of an UD as compared to a SIB was not statistically significant (RR 1.2, p=0.4). When stratified for negative predictors, the actuarial 5 year survival of SIB and UD transplants was 91% vs 81% in low risk patients (n=541, 0-1 negative predictors, p=0.052), 74% vs 72% for the largest group of intermediate risk patients (n=829, 2-3 negative predictors, p=0.4) and 53% vs 50% for a small group of high risk patients (n=130, 4 negative predictors, p=0.8).

This study suggests that the outcome of UD and SIB transplant for SAA is currently comparable, if one corrects for confounding variables, and especially time to transplant. This information warrants the activation of an unrelated donor search for all patients lacking an HLA matched sibling, up to the age of 60, and this may be relevant for treatment strategies.

No relevant conflicts of interest to declare.