Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis

Abstract

We have analyzed 1448 patients with acquired aplastic anemia grafted between 2005 and 2009, and compared outcome of identical sibling (n=940) versus unrelated donor (n=508) transplants. When compared to the latter, sibling transplants were less likely to be performed beyond 180 days from diagnosis (39% vs. 85%), to have a cytomegalovirus negative donor/recipient status (15% vs. 23%), to receive antithymocyte globulin in the conditioning (52% vs. 61%), and more frequently received marrow as a stem cell source (60% vs. 52%). Unrelated donor grafts had significantly more acute grade II-IV (25% vs. 13%) and significantly more chronic graft-versus-host disease (26% vs. 14%). In multivariate analysis, the risk of death of unrelated donor grafts was higher, but not significantly higher, compared to a sibling donor (P=0.16). The strongest negative predictor of survival was the use of peripheral blood as a stem cell source (P<0.00001), followed by an interval of diagnosis to transplant of 180 days or more (P=0.0005), patient age 20 years or over (P=0.0005), no antithymocyte globulin in the conditioning (P=0.003), and donor/recipient cytomegalovirus sero-status, other than negative/negative (P=0.04). In conclusion, in multivariate analysis, the outcome of unrelated donor transplants for acquired aplastic anemia, is currently not statistically inferior when compared to sibling transplants, although patients are at greater risk of acute and chronic graft-versus-host disease. The use of peripheral blood grafts remains the strongest negative predictor of survival.

Figure 1.

Cumulative incidence of acute (A) and chronic (B) graft-versus-host disease (GvHD): a higher rate is seen for both in patients grafted from unrelated as compared to HLA identical sibling donors.

Figure 2.

Univariate analysis of survival in patients with acquired aplastic anemia stratified for stem cell source, (BM: bone marrow; PB: peripheral blood) (A) age 20 years (B), interval between diagnosis transplant (DxTx) 180 days (d), (C) and use of antithymocyte globulin (ATG) in the conditioning regimen (D).

Figure 3.

Survival of patients stratified into 3 risk groups according to prognostic variables (stem cell source, interval diagnosis transplant, age, use of antithymocyte globulin (ATG) and cytomegalovirus (CMV) status): low risk, intermediate risk, and high risk (A). The effect of donor type (UD vs. SIB) is significant in low-risk patients (B); there is no statistical difference between intermediate-risk (C) and high-risk patients (D).