Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

Over the years, sources of grafts in allogeneic hematopoietic stem-cell transplantation have evolved from bone marrow to filgrastim-stimulated peripheral blood, which has a much higher content of blood progenitor cells. Several large, randomized trials of transplantation between HLA-identical siblings showed that peripheral-blood stem cells resulted in better engraftment, but increased the risk of acute and chronic graft-versus-host disease (GVHD) as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.

This open-label, phase 3, multicenter, randomized trial [N Engl J Med. 2012;367(16):1487-1496] was conducted by the Blood and Marrow Transplant Clinical Trials Network; the objective of the trial was to determine the effects of graft source for unrelated-donor transplants by comparing the outcomes of peripheral-blood stem cell and bone marrow transplantations. The investigators enrolled a total of 551 patients between March 31, 2004, and September 9, 2009. The analysis included data collected as of November 15, 2011.

The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). Primary end point was 2-year survival as assessed by means of an intention-to-treat analysis. Prespecified secondary end points included post-transplantation incidences of neutrophil and platelet engraftment, graft failure, acute and chronic GVHD, relapse, and infections.

Eligible patients were <66 years of age and were planning to undergo transplantation for acute leukemia, myelodysplasia, chronic myeloid or myelomonocytic leukemia, or myelofibrosis. These diseases accounted for approximately 75% of unrelated-donor transplantations in the United States during the study period. Patients were followed in the study for 3 years, with a late analysis at 5 years planned with the use of data from the Center for International Blood and Marrow Transplant Research.

Patients were treated in 48 transplantation centers in the United States and Canada. Donors were from 54 National Marrow Donor Program–affiliated donor centers in the United States, Canada, and Germany. The bone marrow and peripheral-blood groups were well balanced with respect to age, sex, Karnofsky performance status score, diagnosis, disease risk, positive result on serologic testing for CMV, and race. The proportion of donors who were fully matched for HLA-A, B, C, and DRB1 and other donor characteristics were similar between the 2 study groups.

Two-year overall survival rate in the peripheral-blood group was 51% (95% confidence interval [CI], 45-57), as compared with 46% (95% CI, 40-52) in the bone marrow group (stratified odds ratio, 1.20; 95% CI, 0.85-1.70). The absolute difference in overall survival at 2 years was 5 percentage points (95% CI, −3-14).

Among patients randomly assigned to receive peripheral-blood stem cells, as compared with those randomly assigned to receive bone marrow, median time to neutrophil engraftment was 5 days shorter (P<.001), and median time to platelet engraftment was 7 days shorter (P<.001).

Primary graft failure occurred in 2% of the patients randomly assigned to receive peripheral-blood stem cells and in 6% of those randomly assigned to receive bone marrow; secondary graft failure occurred in 1% and 3% of patients, respectively. The total incidence of graft failure was 3% (95% CI, 1-5) in the peripheral-blood group and 9% (95% CI, 6-13) in the bone marrow group (P=.002).

The between-group difference in the incidence of all graft failures was 7 percentage points (95% CI, 2-11; P=.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45-61), as compared with 41% (95% CI, 34-48) in the bone marrow group (P=.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.

In conclusion, the researchers stated, “We did not detect significant survival differences between peripheral-blood stem cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD.”