Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogeneic marrow transplantation

Abstract

We have studied the impact of cell dose on short- and long-term graft function and outcome in 905 patients undergoing an unmanipulated allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling (n = 735), a one-antigen mismatched related donor (n = 35), or a matched unrelated donor (n = 135). Median number of nucleated cells infused was 3.4 × 108/kg (25th percentile 2.4 × 108/kg, 75th percentile 5 × 108/kg). Patients were stratified according to cells infused in 3 groups: ≤ 2.4 × 108/kg (n = 247; low dose); >2.4 × 108/kg and ≤ 5 × 108/kg (n = 452; intermediate dose); and >5 × 108/kg (n = 206; high dose). Patients receiving high cell dose had significantly higher platelet counts on days +20, +50, +100, +180, and +365 after BMT (P< .01) and higher white blood cell counts on days +50, +100, and +180 after BMT (P < .01) as compared with other patients. The actuarial 5-year transplant-related mortality (TRM) was 41% versus 36% versus 28% (P = .01); overall survival was 45% versus 51% versus 56% (P = .0008); and disease-free survival was 41% versus 42% versus 48%, respectively, (P = .04) in patients receiving low, intermediate, or high cell dose. The cell dose effect was more pronounced in patients older than 30 years of age, with advanced disease, with chronic myeloid leukemia, and with alternative donors. In multivariate Cox analysis on TRM, cell dose was a significant predictor (P = .002; relative risk 0.6) together with donor type (P = .0001), year of transplantation (P = .0001), conditioning regimen (P = .02), and recipient age (P = .02). In conclusion, transplantation of high marrow cell dose is associated with reduced transplant mortality and improved survival and results in improved graft function both short and long term.