Page 1711 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 95 Practical Aspects of Hematologic Stem Cell Harvesting and Mobilization 1521

for storage with either in utero or ex utero collection techniques. The
timing of cord clamping after delivery of the infant is associated with
the volume of cord blood collected, and greater volumes are collected
with earlier clamping. Greater cell quantities were found for infants
with greater birth weight, but no difference was found based on
gender or gestational age. Ethnic background appears to predict the
cell quantities, with smaller quantities of cells collected from ethnic
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minorities compared with whites. UCB is usually collected by can-
nulation of the umbilical cord veins with aspiration of the blood into
a collection bag. Collection of cord blood into open containers results
in an unacceptable rate of bacterial contamination. Perfusion of the
placenta with salt solutions may increase the cell number collected,
but this technique has not been widely adopted. Many cord blood
banks reduce the volume of the product by red cell and plasma
depletion to minimize storage space and to reduce possible infusion-
related toxicities from mature blood cells contained in unfractionated
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cord blood units. Bacterial contamination of UCB products is of
concern, especially in the collection of products for related donor
Fig. 95.2 Kaplan-Meier plots of time to recovery from stem cell donation transplantation by obstetricians with limited or no experience in
(first donations performed from November 2001 through March 2006). HSC collection and processing. The identification and evaluation
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(From Biol Blood Marrow Transplant. 14[9 Suppl]:29–36, 2008, doi: 10.1016/j. of the donor and the collection techniques used should be viewed as
bbmt.2008.05.018.)
the first steps in a manufacturing process with adequately validated
procedures, personnel training, quality control, and performance
improvement oversight.
autologous patients may be greater, reflecting previous chemotherapy
given to these patients causing decreased marrow cellularity. Donors
for pediatric recipients will lose proportionately less blood. Most
patients and donors receive blood transfusions to alleviate symptoms COLLECTION OF PERIPHERAL BLOOD STEM CELLS
of volume depletion. With proper preharvest autologous blood FOR TRANSPLANTATION
storage, use of homologous blood for healthy first-time allogeneic
donors should be extremely rare. For a blood loss of less than 10 mL/ Background
kg of donor weight, salt solutions are acceptable for volume replace-
ment. Colloid solutions, such as hydroxyethyl starch, can be used to The presence of HSCs in the peripheral circulation was suggested by
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avoid homologous blood transfusion for blood losses between 10 and animal studies as early as 1951. Although the nature of the survival
20 mL/kg donor weight. Blood transfusion will be required for larger agent was not recognized at that time, parabiosis experiments dem-
blood losses (>20 mL/kg) or for patients with comorbid illnesses. onstrated that some factor in the blood of a healthy animal was able
Homologous blood transfusions must be irradiated to prevent to rescue another animal from the effects of lethal irradiation. Sub-
transfusion-associated GVHD in the transplant recipient caused by sequently, a number of animal models demonstrated the presence of
“passenger lymphocytes” from the third-party blood donor. Donors HSCs in the peripheral blood and the successful use of these cells to
undergoing a second harvest shortly after the first harvest are more rescue animals from the marrow-lethal effects of radiation. The
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likely to require homologous blood. Oral iron supplements should concentration of HSCs in the peripheral blood is normally very low,
be considered for healthy donors, particularly for female donors or requiring the processing of large quantities of blood to collect the
donors from whom a proportionately large blood volume is to be quantity of HSCs equivalent to what could be collected in a bone
harvested. marrow harvest. For this reason, PBSC transplantation was initially
used by a few transplant programs that explored this source of HSCs
for patients who otherwise were ineligible for marrow harvesting,
COLLECTION OF UMBILICAL CORD BLOOD STEM CELLS collecting cells during steady-state hematopoiesis or during the
transient increase in circulating HSCs that occurred during recovery
FOR TRANSPLANTATION from marrow hypoplasia-producing chemotherapy. 49–53 These early
reports noted that engraftment could be achieved sooner after infu-
Cord Blood Collection Techniques sion of PBSC components compared with marrow cell transplanta-
tion. However, because of the occasionally limited quantity of HSCs
Advantages of this source of HSCs include the ability of public cord that was collected from the peripheral blood, the kinetics of engraft-
blood banks to target collections from ethnic-minority populations ment for some patients was considerably slower. The effective
not well represented in the various unrelated donor registries and the mobilization of HSCs achieved by cytokine or chemokine adminis-
relative immaturity of the donor immune system allowing transplan- tration, 54–56 and the reliability of same-day flow cytometric analysis
tation of HLA-mismatched units without overwhelming GVHD. in assessing the quality of the collection, are the direct bases for the
The primary obstacle to the widespread use of cord blood cells is the rapid and widespread adoption of PBSCs as a source of HSCs for
limited quantity of HSCs collected, and one public UCB bank pre- transplantation (see box on Mobilization and Collection of Peripheral
dicted that from less than 5% to less than 38% (depending on the Blood Stem Cell for Autologous Transplantation).
cell dose criterion for transplantation) of the units stored in that bank
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would be acceptable for transplantation of an 80-kg adult patient.
The speed and success of engraftment are predicted by the total Mobilization of Hematopoietic Stem
+
nucleated cell dose and, more important, by the quantity of CD34 Cells Into Peripheral Blood
cells or infused colony-forming units (CFUs). 44
UCB is collected from the placental vein after delivery of the The self-renewal and differentiation of HSCs is controlled by the
infant and transection of the cord, either before delivery of the pla- surrounding microenvironment of the stem cell niche(s) in which the
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centa by the obstetrician or by laboratory personnel after delivery of HSC reside. These niches are composed of a complex three-
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the placenta. Published reports conflict regarding the volume of dimensional architecture of a variety of cell types including sinusoidal
UCB collected and the likelihood of obtaining a product inadequate endothelial cells, sympathetic nerve fibers, cells of the osteoblastic