Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis

Abstract

Background: Umbilical-cord blood (UCB) is increasingly considered as an alternative to peripheral blood progenitor cells (PBPCs) or bone marrow, especially when an HLA-matched adult unrelated donor is not available. We aimed to determine the optimal role of UCB grafts in transplantation for adults with acute leukaemia, and to establish whether current graft-selection practices are appropriate.

Methods: We used Cox regression to retrospectively compare leukaemia-free survival and other outcomes for UCB, PBPC, and bone marrow transplantation in patients aged 16 years or over who underwent a transplant for acute leukaemia. Data were available on 1525 patients transplanted between 2002 and 2006. 165 received UCB, 888 received PBPCs, and 472 received bone marrow. UCB units were matched at HLA-A and HLA-B at antigen level, and HLA-DRB1 at allele level (n=10), or mismatched at one (n=40) or two (n=115) antigens. PBPCs and bone-marrow grafts from unrelated adult donors were matched for allele-level HLA-A, HLA-B, HLA-C, and HLA-DRB1 (n=632 and n=332, respectively), or mismatched at one locus (n=256 and n=140, respectively).

Findings: Leukaemia-free survival in patients after UCB transplantation was comparable with that after 8/8 and 7/8 allele-matched PBPC or bone-marrow transplantation. However, transplant-related mortality was higher after UCB transplantation than after 8/8 allele-matched PBPC recipients (HR 1.62, 95% CI 1.18-2.23; p=0.003) or bone-marrow transplantation (HR 1.69, 95% CI 1.19-2.39; p=0.003). Grades 2-4 acute and chronic graft-versus-host disease (GvHD) were lower in UCB recipients compared with allele-matched PBPC (HR 0.57, 95% 0.42-0.77; p=0.002 and HR 0.38, 0.27-0.53; p=0.003, respectively), while the incidence of chronic, but not acute GvHD, was lower after UCB than after 8/8 allele-matched bone-marrow transplantation (HR 0.63, 0.44-0.90; p=0.01).

Interpretation: These data support the use of UCB for adults with acute leukaemia when there is no HLA-matched unrelated adult donor available, and when a transplant is needed urgently.

Figure 1

A. The probabilities of neutrophil recovery by HSC source: the day-42 probability of neutrophil recovery after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 80%, 96%, 92%, 96% and 94%, respectively B. The probabilities of platelet recovery by HSC source: the 6-month probability of platelet recovery after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 63%, 88%, 82%, 80% and 84%, respectively

Figure 1

A. The probabilities of neutrophil recovery by HSC source: the day-42 probability of neutrophil recovery after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 80%, 96%, 92%, 96% and 94%, respectively B. The probabilities of platelet recovery by HSC source: the 6-month probability of platelet recovery after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 63%, 88%, 82%, 80% and 84%, respectively

Figure 2

The probabilities of leukemia-free survival by HSC source and donor-recipient HLA-match, adjusted for disease status at transplantation: the 2-year adjusted probability of leukemia-free survival after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 33%, 39%, 41%, 34% and 34%, respectively.

Figure 3

A. The probabilities of leukemia-free survival by HSC source and donor-recipient HLA-match for patients in remission at transplantation: the 2-year probability of leukemia-free survival after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 44%, 50%, 52%, 39% and 41%, respectively B. The probabilities of leukemia-free survival by HSC source and donor-recipient HLA-match for patients who were not in remission at transplantation: the 2-year probability of leukemia-free survival after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 15%, 17%, 17%, 17% and 14%, respectively

Figure 3

A. The probabilities of leukemia-free survival by HSC source and donor-recipient HLA-match for patients in remission at transplantation: the 2-year probability of leukemia-free survival after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 44%, 50%, 52%, 39% and 41%, respectively B. The probabilities of leukemia-free survival by HSC source and donor-recipient HLA-match for patients who were not in remission at transplantation: the 2-year probability of leukemia-free survival after transplantation of 4-6/6 HLA matched UCB, 8/8 HLA matched PBPC, 8/8 HLA matched BM, 7/8 HLA matched PBPC and 7/8 HLA matched BM was 15%, 17%, 17%, 17% and 14%, respectively