Sources of Hematopoietic Stem Cells: Peripheral Blood

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The page below is a sample from the LabCE course Hematopoietic Stem Cell Transplantation. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Sources of Hematopoietic Stem Cells: Peripheral Blood

HSC transplantation from apheresis of peripheral blood after stimulation with hematopoietic growth factors has become the most common source of allogeneic transplants. Preliminary testing of the peripheral blood stem cell (PBSC) donor is similar to bone marrow donors. Growth factors, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-stimulating factor (GM-CSF), stimulate the bone marrow to release HSCs and early progenitor cells which can be collected by apheresis.
Apheresis is an automated procedure that separates the white cells and platelets from the red cells and plasma. The mononuclear CD34 positive cells in the buffy coat are separated from the other cells and collected in a sterile collection bag containing anticoagulant citrate dextrose (ACD-A). The procedure takes from 3-5 hours but results in a higher concentration of CD34+ cells than a bone marrow extraction. This procedure is more popular with HLA matched donors because it can take place in an outpatient setting, does not require hospitalization, and eliminates the risk associated with anesthesia. The cryopreservation process is similar to the processing of umbilical cord blood. The most common side effects of apheresis collection of peripheral blood HSCs are bone pain, muscle aches, and headache prior to the collection procedure. These are side effects of the G-CSF injections that disappear after donation.
G-CSF (Filgrastim™, Pegfilgrastim™) is a hematopoietic growth factor that increases production of neutrophils and early progenitor cells. In autologous transplants, G-CSF is combined with chemotherapy to mobilize HSCs. In allogeneic normal donors, G-CSF stimulates the bone marrow to release increased numbers of HSCs into the peripheral blood. The typical donor receives 5 to 10 µg/kg of body weight for a week. The peak concentration of HSCs will occur when the CD34 counts exceed 3 x 106 CD34 positive cells per kg of the recipient's body weight.
GM-CSF, (Sargramostim™) is a hematopoietic growth factor that controls the differentiation of myeloid progenitors into granulocytes, eosinophils, monocytes, megakaryocytes, and erythrocytes. It may be used in combination with G-CSF to improve mobilization of HSCs in donors with low CD34 counts.
In 2008 the FDA approved a new mobilization drug, Plerixafor™, for autologous transplants. Plerixafor™ blocks the action of cytokines that cause HSCs to remain in the bone marrow and increases their release into the peripheral blood. This drug has not been approved for use in normal allogeneic donors, but is being used in autologous donors who do not respond to G-CSF and GM-CSF. In one study, patients with multiple myeloma were treated with G-CSF and Plerixafor™ and had higher CD34 counts than myeloma patients receiving G-CSF alone.