Biomedical Engineering Reference
In-Depth Information
Due to the reasons mentioned above, the number of patients treated by SCs
harvested from PB is increasing worldwide, especially in autologous SC transplant
setting. In order to obtain adequate SC yield, allogeneic donors are given rHuG-
CSF 5-10 mg/kgbm per day. The count of CD34
+
cells in the circulation begins to
rise after the third day, and peaks following 5-6 days of rHuG-CSF administration.
In autologous setting, patients are given higher rHuG-CSF dose (10-16 m g/kgbm
daily) [
6,
38-
40
]. In allogeneic setting, the first apheresis is performed typically on
the fifth day of the rHuG-CSF application. The determination of optimal timing of
an autologous SC harvesting is more complex and controversial. It is suggested as
the optimal point to begin autologous SC collection when the leukocyte count
exceeds 5-10 × 10
9
/L. However, the leukocyte count commonly does not correlate
with the CD34
+
number. The count of circulating CD34
+
cells evidently correlates
with the optimized collection timing, as well as with the superior CD34
+
yield in
harvest. Generally, at peripheral blood CD34
+
count
10/mL, expected SC yield
·1 × 10
6
/kgbm. It is also presented that for a CD34
+
³ 20-40/ mL of peripheral blood
the possibility of the CD34
+
³ 2.5 × 10
6
/kgbm is 15% using one standard apheresis,
and 60% after one large-volume SC harvesting [
36,
38
] .
The target mononuclear cell count in harvest should be 314 × 10
8
per unit, that is,
³ 2-4 × 10
8
/kgbm, and CD34
+
cells should be 330 × 10
6
per unit or ³ 2-4 × 10
6
/kgbm
of the recipient in order to expect successful transplant. However, recent data sup-
port a benefit associated with greater CD34
+
yield (³ 5 × 10
6
/kgbm) compared to the
minimum required cell quantity for engraftment (³ 1 × 10
6
/kgbm) in autologous set-
ting. Finally, results obtained in our SC transplant center confirmed that large-
volume apheresis is efficient (CD34
+
³ 5 × 10
6
/kgbm) if the circulating CD34
+
count
was around 40-60/mL after mobilizing regiment [
6,
38
] . Although are generally
accepted, the stated values of SC yields cannot guarantee stable and long-term BM
repopulation after transplant. In order to achieve them, the following issues are
needed: (a) quantity of processed blood ³2-4 of patient's circulating blood volume
per one apheresis (large-volume leukapheresis), that is, around 12-25 L for person
with around 70-80 kgbm, and/or (b) apheretic procedures should be performed one
to two (occasionally three) times on the average [
5,
38-
40
] (Fig.
9.3
).
Selection of CD34
+
cells is associated with a reduction of count of tumor cells
(autologous) or T-cells (allogeneic) in harvest. Since peripheral blood has become
the major source of mobilized SCs for allogeneic transplant—but with high-level
mononuclear cell contamination—effective technologies for unwanted cell deple-
tion were developed to reduce the risk of disease recurrence or GvHD. The use of
“positive” or “negative” immunomagnetic cell selection has been shown to be the
most effective method to achieve ³ 3-4 Log
10
depletion of tumor or T-cells while
preserving the high number of CD34
+
cells in the harvest. Namely, the CD34
+
cell
recovery (CD34
+
count in comparison with the number present before selection)
should be at least 50-70% and cell purity (ratio of CD34
+
vs. mononuclear cells)
around 70-90% or more [
5,
6,
36
] .
Patients who have been earlier treated with high-dose cytostatics may be poor
responders to SC mobilization protocol with rHuG-CSF plus chemotherapy. The
most efficient approach to obtain a sufficient SC yield in harvest from poorly
≅
