Allogeneic transplantation of CD34+selected cells from peripheral blood from human leukocyte antigen–identical siblings: detrimental effect of a high number of donor CD34+ cells?

Abstract

Clinical results after T-cell–depleted allografts might be improved by modifying the graft content of progenitor and accessory cells. Although the association of the number of donor T cells with the clinical outcome has been studied extensively, the optimum number of progenitor cells that should be administered to patients is unknown. The characteristics of 84 consecutive human leukocyte antigen (HLA)–identical sibling transplants of granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood progenitor cells depleted of T cells by CD34+ positive selection (allo-PBT/CD34+) were analyzed for their effect on clinical outcome. After a median follow-up of 24 months (range, 1-70 months), 50 patients remain alive (59.5%) and 34 have died (21 [25%] as a result of the transplant and 13 [15.5%] due to disease relapse). The median number of CD34+ cells administered to the patients was 3.9 × 106/kg (range, 1.2-14.3 × 106/kg). A number of CD34+ cells in the inoculum of 1 × 106/kg to 3 × 106/kg was associated with increased survival: 21 of 28 (75%) patients are alive, as compared with 29 of 56 (52%) patients receiving more than 3 × 106/kg (actuarial probability 75% vs. 42%, respectively; P = .01). In the multivariate analysis, the independent prognostic variables for survival were CD34+cell dose 1 × 106/kg to 3 × 106/kg (RR = 4.8; P = .0008), sex-pairing match (RR = 3.2;P = .002), and early stage of disease (RR = 2.8;P = .007). From these results it appears that, in allo-PBT/CD34+ from HLA-identical siblings, a number of CD34+ cells in the inoculum between 1 × 106/kg to 3 × 106/kg is an important factor for better survival, and that higher CD34+ cell doses might be associated with a poorer outcome.