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SOURCES OF HEMATOPOIETIC STEM CELLS (HSCs)

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Marrow

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  • Marrow for hematopoietic stem cell transplantation (HSCT) 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, and a standard collection contains more than 2 × 108 nucleated marrow cells/kg recipient body weight.

  • Current guidelines indicate that a volume of up to 20 mL/kg donor body weight should be effective.

  • Seventy percent of donors fully recover by 2 weeks and the risk of serious complications is 1.2 percent.

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Mobilized Peripheral Blood Stem Cells (PBSC)

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  • The most common method to harvest autologous and allogeneic PBSCs is by using granulocyte colony-stimulating factor (G-CSF) with or without chemotherapy. This procedure is safe and in a review of 5930 normal donors, serious side effects were uncommon (< 1%). Splenic rupture has been reported with an estimated incidence of 1 in 10,000.

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

  • 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 PBSC product. A minimum of 2 × 106/kg CD34+ cells is usually recommended, although at this dose, 10 to 20 percent of autologous collections lead to suboptimal (slow or more rarely, no) engraftment. Platelet recovery is most sensitive to borderline collection numbers.

  • Although the number of T cells in 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 percent 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, since 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 HSCs.

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

  • An analysis of approximately 100 UCB transplants showed that recipients who received < 1.7 × 107 cells/kg body weight had a high rate of graft failure. For adults, this usually requires the use of two closely and suitably matched cord bloods providing a higher CD34+ and CD3+ cell dose.

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DEGREE OF MATCHING

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HLA Matched Related Donor

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  • HLA matched sibling donors were the most common source of HSCT products prior to the establishment of sufficiently diverse unrelated stem cell donor banks. The experience with these transplants for ...

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