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SOURCES OF HEMATOPOIETIC STEM CELLS

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Marrow

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  • Marrow for hematopoietic cell transplantation (HCT) is typically aspirated by repeated placement of large-bore needles into the posterior iliac crest, generally 50 to 100 aspirations simultaneously on both sides, while under regional or general anesthesia.

  • The lowest cell dose to ensure stable long-term engraftment has not been defined with certainty. Typical collections contain more than 2 × 108 total nucleated marrow cells/kg recipient body weight.

  • Current guidelines indicate that a volume of up to 20 mL/kg donor body weight is considered safe.

  • The risk of serious complications is about 2%.

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Peripheral Blood Progenitor Cells

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  • The most common method to harvest autologous peripheral blood progenitor cells (PBPCs) is by using granulocyte colony-stimulating factor (G-CSF) with or without chemotherapy. In contrast, PBPCs for allogeneic HCT are typically mobilized with G-CSF alone. This procedure is safe and in a review of nearly 7000 healthy unrelated donors, serious side effects were uncommon (< 1%). Splenic rupture is extremely rare.

  • The measurement of the absolute number of CD34+ cells/kg recipient body weight collected is a reliable and practical method for determining the adequacy of the PBPC product. A minimum of 2 × 106/kg CD34+ cells is usually recommended, although at this dose, 10% to 20% of autologous collections lead to suboptimal (slow, or more rarely, no) engraftment. Platelet recovery is most sensitive to borderline collection numbers.

  • Randomized clinical trials have indicated that engraftment is more rapid with PBPCs than with marrow-derived stem cells.

  • Although the number of T cells in peripheral blood stem cell (PBSC) graft is 10-fold greater than in marrow, the incidence of acute graft-versus-host disease (GVHD) does not appear higher, probably because G-CSF influences the proportion of immune tolerizing Treg cells in the apheresis product. However, the risk of chronic GVHD has been found to be about 10% higher in PBSC at most major transplant centers.

  • The use of G-CSF to mobilize stem cells in patients with sickle cell anemia is contraindicated, because an acute increase in neutrophil counts can precipitate a catastrophic sickle cell occlusive crisis.

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Umbilical Cord Blood

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  • Umbilical cord blood (UCB) collected from the umbilical vessels in the placenta at the time of delivery is a rich source of hematopoietic stem cells (HSCs).

  • Because these cells are immunologically relatively naive, recipients may have satisfactory outcomes, even when crossing major histocompatibility barriers.

  • The minimum acceptable cell dose for single-unit UCB transplantation is greater than or equal to 2.5 × 107 total nucleated cells or greater than or equal to 2 × 105 CD34+ cells/kg recipient weight. For adults, this usually requires the use of two suitably matched cord bloods, providing a higher total CD34+ dose.

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DEGREE OF MATCHING

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Human Leukocyte Antigen (HLA)-Matched Related Donor

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  • HLA-matched sibling donors were the most common source of HCT products prior to the ...

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