CD34+ Hematopoietic Stem Cells Are Collected During Stem Cell Mobilization
During hematopoietic stem cell mobilization, CD34+ hematopoietic stem cells are collected from the peripheral blood. 1 These CD34+ cells represent the hematopoietic progenitor cells that have the ability to self-renew and differentiate into all blood cell lineages.
Characteristics of CD34+ Hematopoietic Stem Cells
CD34+ cells have several important properties:
- They are pluripotent cells capable of producing all types of blood cells
- They possess self-renewal capabilities
- They represent a small fraction (1-4%) of bone marrow cells 2
- They comprise virtually all hematopoietic colony-forming progenitors in vitro
- They are capable of restoring hematopoiesis in patients following myeloablative therapy
Mobilization Process and Collection
The mobilization of CD34+ cells into peripheral blood is achieved through:
Single-agent growth factor approach: Using G-CSF (granulocyte colony-stimulating factor) at doses of 10-32 mcg/kg/day by subcutaneous injection, with apheresis beginning on day 4 or 5 1
Chemomobilization approach: Combining G-CSF with chemotherapy (e.g., cyclophosphamide, ICE, DHAP), with G-CSF started approximately 24 hours after completion of chemotherapy 1
Combination approach: Using G-CSF with plerixafor for patients who are heavily pretreated or at risk of being poor mobilizers 1
Source of Stem Cells
While both bone marrow and peripheral blood can serve as sources for hematopoietic stem cells, peripheral blood stem cells (PBSCs) have largely replaced bone marrow collection for autologous transplantation due to:
- Ease of collection
- Avoidance of general anesthesia
- More rapid recovery of blood counts 1
- Faster engraftment of neutrophils and platelets 1
- Potential reduction in malignant cell contamination of the autograft 1
The NCCN guidelines favor peripheral blood stem cells as the stem cell source based on differences in outcomes affected by engraftment rate 1.
Clinical Implications and Considerations
Several important clinical considerations should be kept in mind:
Previous exposure to alkylating agents: May reduce the ability to harvest sufficient stem cells. It is prudent to avoid exposure to melphalan before stem-cell collection when transplantation is a consideration 1
Timing of collection: Early collection of stem cells (after 4 cycles of therapy) is recommended, particularly for patients receiving lenalidomide, as prolonged exposure may decrease the number of CD34+ cells collected 1
Quantification: Accurate quantification of CD34+ cells is essential for successful transplantation. Flow cytometric methods are used to enumerate these cells in harvested products 3
Target cell dose: The target mononuclear cell count for transplantation is typically 6 × 10^8/kg of recipient weight 1
Clinical Applications
CD34+ hematopoietic stem cells collected during mobilization are used for:
- Autologous stem cell transplantation for various malignancies
- Allogeneic transplantation from related or unrelated donors
- Treatment of a variety of cancers and blood disorders including leukemia, lymphoma, myelodysplastic syndromes, and myeloproliferative disorders 4
The ability to collect adequate numbers of CD34+ cells is crucial for successful engraftment and reconstitution of hematopoiesis following myeloablative therapy.