Enumeration of bone marrow 'homing' haemopoietic stem cells from G-CSF-mobilised normal donors and influence on engraftment following allogeneic transplantation.
Expression of the chemokine receptor CXCR4 on human haemopoietic stem cells (HSC) may play a crucial role in localising these cells to the bone marrow. To evaluate whether CXCR4 expression is clinically relevant we have enumerated CXCR4-positive HSC used for allogeneic transplantation and sought any relationship with the rate of subsequent haemopoietic reconstitution. CD34-positive progenitor cells were isolated from peripheral blood stem cell (PBSC) collections from 16 normal donors. The proportion of cells co-expressing CXCR4 was enumerated and the times to recipient haemopoietic reconstitution measured. The median frequency of CD34-positive cells co-expressing CXCR4 was 41% (range 16% to 76%) and the median number of CXCR4 CD34 double-positive cells infused at transplantation was 2.5 x 10(6) cells/kg (range 0.8-10.3). Patients receiving >2.5 x 10(6) CXCR4 CD34 double-positive cells/kg demonstrated a significant shortening of time to platelet engraftment compared to the recipients of the lower cell doses (10 days vs 14.5 days, respectively, P = 0.02) with all but one of the recipients of the higher cell doses achieving platelet engraftment by day 11. Co-expression of CXCR4 on CD34-positive progenitor cells may be an important determinant of post-transplant engraftment and in our hands transplantation of a minimum of 2.5 x 10(6) CXCR4 CD34 double-positive cells/kg ensured rapid post-transplant platelet recovery.
Spencer
A
A
BMT Programme, Alfred Hospital, Melbourne, Victoria, Australia.
Jackson
J
J
Baulch-Brown
C
C
D000328:Adult; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count / Q000379:methods; D014019:Tissue Donors; D014184:Transplantation, Homologous
D016179:Granulocyte Colony-Stimulating Factor