Transplantation of Filgrastim-Mobilized Peripheral Blood Stem Cells From HLA-Identical Sibling or Alternative Family Donors in Patients With Hematologic Malignancies: A Prospective Comparison on Clinical Outcome, Immune Reconstitution, and Hematopoietic Chimerism

Abstract

Abstract The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts <500/μL (13 v 17 days) or <1,000/μL (16 v 19 days) and unsupported platelet counts <20,000/μL (11 v 15 days) or <50,000/μL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% ± 10% but ranged between 86% ± 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% ± 9% in recipients of GVHD-matched transplants (P < .003). The 2-year survival estimates were 54% ± 10% for patients with alternative family donors and 65% ± 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.