ALLOGENEIC BLOOD STEM-CELL TRANSPLANTATION - PERIPHERALIZATION AND YIELD OF DONOR-DERIVED PRIMITIVE HEMATOPOIETIC PROGENITOR CELLS (CD34(-1(DIM)) AND LYMPHOID SUBSETS, AND POSSIBLE PREDICTORS OF ENGRAFTMENT AND GRAFT-VERSUS-HOST DISEASE() THY)

Apheresis-derived hematopoietic progenitor cells have recently been us ed for allogeneic transplantation. Forty-one normal donors were studie d to assess the effects of recombinant human granulocyte colony-stimul ating factor (rhG-CSF) (12 mu g/kg/d) on the peripheralization of hema topoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the p eak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded ba seline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concen trations of PB CD34(+) cells and primitive subsets such as CD34(+) Thy -1(dim), and CD34(+) Thy-1(dim) CD38(-) cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The per centage of CD34(+) Thy-1(dim) and CD34(+) Thy-1(dim) CD38(-) cells amo ng CD34(+) cells increased as well, suggesting an additional periphera lization effect of rhG-CSF on primitive CD34(+) subsets. The preaphere sis PB CD34(+) and CD34(+) Thy-1(dim) cell concentrations were predict ive of their corresponding apheresis yield per liter of donor blood pr ocessed. PB lymphoid subsets were not significantly affected by rhG-CS F treatment. The mean apheresis-derived yield of CD34(+), CD34(+) Thy- 1(dim) and CD34(+) Thy-1(dim) CD38(-) cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvests, the CD34(+) cel l yield of peripheral blood progenitor cell allografts of 41 normal do nors exceeded that of BM allografts by 3.7-fold and that of lymphoid s ubsets by 16.1-fold (CD3(+)), 13.3-fold (CD4(+)), 27.4-fold (CD8(+)), 11.0-fold (CD19(+)), and 19.4-fold (CD56(+)CD3(-)). All PBPC allograft s were cryopreserved before transplantation. The mean recovery of CD34 (+) cells after freezing, thawing, and washing out dimethylsulfoxide w as 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3 (+)), 121.4% (CD4(+)), 105.6% (CD8(+)), 118.1% (CD19(+)), and 102.4% ( CD56(+)CD3(-)). All donors were related to patients: 39 sibling-to-sib ling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eigh t transplants were HLA fully identical, two transplants differed in on e and two antigens. Engraftment occured in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34(+) cell dose transplanted and resulting in complete and su stained engraftment was 2.5 x 10(6)/kg of recipient body weight. There was no significant correlation between the total number of CD34(+) ce lls transfused and the time to reach PMNC > 0.5 x 10(9)/L or platelets > 50 x 10(9)/L posttransplant, nor was there a correlation found betw een the total number of CD3(+), CD4(+), and CD8(+) cells transfused an d the development of acute graft-versus-host disease (GVHD). The actua rial probability of developing acute GVHD in 38 evaluable patients was 48%. In 13 patients followed longer than 100 days posttransplant, the actuarial probability of developing chronic GVHD was 66% (median foll ow-up, 264 days). (C) 1995 by The American Society of Hematology.