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

The clinical results, cellular immune reconstitution, and hematopoieti c chimerism obtained after transplantation of recombinant human granul ocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-id entical sibling (n = 36) or alternative family donors in = 24) were pr ospectively compared in patients with hematologic malignancies. Thirty -two of 34 evaluable patients with HLA-identical sibling donors and al l patients with alternative family donors achieved trilineage engraftm ent. The median time intervals to reach peripheral neutrophil counts > 500/mu L (13 v 17 days) or >1,000/mu L (16 v 19 days) and unsupported platelet counts >20,000/mu L (11 v 15 days) or >50.000/mu L(19 v 24 da ys) as well as red blood cell and platelet transfusion requirements we re not significantly different between both patient subsets. The cumul ative probability of grades II through IV acute graft-versus-host dise ase (GVHD) for the 60 study patients was 48% +/- 10% but ranged betwee n 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 re cipients of GVHD-matched transplants (P <.003). The 2-year survival es timates were 54% +/- 10% for patients with alternative family donors a nd 65% +/- 9% for patients with HLA-identical sibling donors. Multivar iate 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 b lood T-helper cell subsets, B cells, and monocytes during the first ye ar posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences i n the proportions of complete chimeric patients were detectable betwee n the two patient subsets by sex chromosome and variable number of tan dem repeats analysis up to 12 months posttransplantation. In conclusio n, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibl ing donors and should be further evaluated in comparison with marrow t ransplants from alternative family donors. (C) 1997 by The American So ciety of Hematology.