Comparison of the content and subpopulations of CD3 and CD34 positive cells in bone marrow harvests and G-CSF-mobilized peripheral blood leukapheresis products from healthy adult donors.
Recombinant human granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem/progenitor cells (PBPC) have replaced bone marrow (BM) harvests for autologous transplantation after myeloablative therapy in cancer patients. G-CSF-mobilized PBPC from healthy donors contain one log excess of T lymphocytes representing a potential risk for graft-versus-host disease (GVHD). However, recent pilot clinical studies of G-CSF-mobilized allogeneic PBPC transplantation have shown rapid haematological recovery and no severe acute GVHD except in a very few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected during the pioneering period of allogeneic PBPC transplantation. The present study was performed to address the possible reasons for the rapid haematological recovery and the absence of severe acute GVHD observed after allogeneic PBPC transplantation by comparing the contents and subsets of CD3+ and CD34+ G-CSF-mobilized PBPC (n = 31) with those of BM (n = 26) allografts from healthy adult donors. The present results revealed that the phenotypic profiles of CD3+ and CD34+ cells differ between PBPC and BM allografts. The single PBPC leukapheresis product contained 10 times more mononuclear cells, 1.5 times more CD34+ cells, 5.5 times more CD3+ T lymphocytes, 3 times more CD19+ B lymphocytes and 3.8 times more CD14+ monocytes than the single BM harvest. Both CD34+CD33+ myeloid progenitor cells and CD34+HLA-DR-long-term reconstituting haemopoietic stem cells were significantly increased in the CD34+ G-CSF-mobilized PBPC compared with the CD34+ BM cells; median 73.1% and 30.4% vs 60.6% and 5.0%, respectively, P < 0.01. The percentage of CD3+ cells coexpressing CD4 (T helper/inducer) was similar in both PBPC and BM allografts, 47.2% and 45.6%, respectively, whereas the percentage of CD3+ cells coexpressing CD8 (T suppressor/cytotoxic) was significantly decreased in PBPC compared with BM; 37.0% vs 55.9%, p < 0.01. The rapid haematological recovery after allogeneic PBPC transplantation could be due to the increased content of CD34+CD33+ myeloid committed cells and the CD34+HLA-DR-long-term reconstituting haemopoietic stem cells in the PBPC allografts. Also, the absence of an increased risk of severe acute GVHD after allogeneic PBPC transplantation could be due to the increased T lymphocyte ratio of CD4+/CD8+ in the PBPC allografts. In conclusion, rapid haematological recovery without an increased risk of severe acute GVHD can be achieved using G-CSF-mobilized PBPC rather than BM for allogeneic transplantation.
Hassan
H T
HT
Bone Marrow Transplantation Center, Hamburg University Hospital Eppendorf, Germany.
Stockschläder
M
M
Schleimer
B
B
Krüger
W
W
Zander
A R
AR
D000328:Adult; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D002452:Cell Count; D000069585:Filgrastim; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000145:classification* / Q000187:drug effects; D006801:Humans; D007937:Leukapheresis; D018655:Lymphocyte Count; D008875:Middle Aged; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D016896:Treatment Outcome
D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim