Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups

Abstract

Background: Bone marrow has been shown to be superior to peripheral blood, as a stem cell source, in young patients (<20 years of age) with acquired aplastic anemia undergoing a matched sibling transplant. The aim of this study was to test whether this currently also holds true for older patients with acquired aplastic anemia.

Design and methods: We analyzed 1886 patients with acquired aplastic anemia who received a first transplant from a human leukocyte antigen identical sibling between 1999 and 2009, with either bone marrow (n=1163) or peripheral blood (n=723) as the source of stem cells.

Results: In multivariate Cox analysis negative predictors for survival were: patient's age over 20 years (RR 2.0, P<0.0001), an interval between diagnosis and transplantation of more than 114 days (RR 1.3, P=0.006), no anti-thymocyte globulin in the conditioning (RR 1.6, P=0.0001), a conditioning regimen other than cyclophosphamide (RR=1.3, P=0.008) and the use of peripheral blood as the source of stem cells (RR 1.6, P<0.00001). The survival advantage for recipients of bone marrow rather than peripheral blood was statistically significant in patients aged 1-19 years (90% versus 76% P<0.00001) as well as in patients aged over 20 years (74% versus 64%, P=0.001). The advantage for recipients of bone marrow over peripheral blood was maintained above the age of 50 years (69% versus 39%, P=0.01). Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants. Major causes of death were graft-versus-host disease (2% versus 6% in bone marrow and peripheral blood recipients, respectively), infections (6% versus 13%), and graft rejection (1.5% versus 2.5%).

Conclusions: This study shows that bone marrow should be the preferred stem cell source for matched sibling transplants in acquired aplastic anemia, in patients of all age groups.

Figure 1.

Incidences of acute and chronic GvHD expressed as percentages. Patients receiving peripheral blood (PB-hashed bars) transplants had significantly higher risks of acute GvHD grade II–IV, III–IV, overall chronic GvHD and extensive chronic GvHD, as compared to patients receiving bone marrow (BM-black bars).

Figure 2.

Actuarial survival for the whole cohort of patients stratified, in univariate analysis, according to: (A) the interval between diagnosis and transplantation (

Figure 3.

Actuarial survival of patients receiving peripheral blood (PB) or bone marrow (BM) transplants, and stratified by age: (A) <20 years or (B) ≥20 years of age. The difference is statistically significant in both groups.

Figure 4.

(A) Actuarial survival of all patients stratified by negative predictors of survival: interval diagnosis-transplant (Dx-Tx) ≥114 days, recipients’ age ≥20 years, no anti-thymocyte globulin (ATG) in the conditioning, a conditioning regimen other than cyclophosphamide 200 mg/kg. Three groups were identified: low risk (survival 89%), intermediate risk (survival 78%) and high risk (survival 64%). (B) Actuarial survival for BM vs PB graft recipients in the low risk group (P=0.0001); (C) Actuarial survival for BM vs. PB graft recipients in the intermediate risk group (P=0.02); (D) Actuarial survival for BM vs. PB graft recipients in the high risk group (P=0.006).