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M
obilization
of hematopoietic
progenitor
cells
for
autologous
transportation
:
consensus
recommendations
to our reality and that could serve as a starting point for
broader efforts to improve clinical outcomes of patients
submitted to autologous hematopoietic stem cell trans-
plantation from peripheral blood in Brazil.
P
redictive
factors
of
poor mobilization
The identification of risk factors associated with the
disease and the patient that can predict poor mobilization
of hematopoietic progenitor cells is of utmost importance
for the optimization of both the therapy and resource
allocation. Several studies carried out to investigate this
question showed that the diagnosis of lymphoma,
14-19
thrombocytopenia,
14,20-23
older age
18-21,23-25
and polytreat-
ment
14,16,19,25,26
, among other factors, emerged as the main
potential factors for the prediction of poor recruitment of
hematopoietic stem cells.
However, the retrospective characteristic of these stu-
dies, the relatively low number of assessed patients, the
heterogeneity of the studied populations, the use of diffe-
rent mobilization regimens and lack of uniform criteria for
the definition of failure contributed to the achievement of
conflicting results,
11,27-29
making data interpretation and the
drawing of definitive conclusions about the role of these
factors in therapeutic decision-making difficult. The most
robust factor for the prediction of collection efficiency is
the CD34+ cell count in peripheral blood before aphere-
sis and its implementation in daily practice has the added
potential to save financial resources.
7,30-34
Recommendation: the isolated use of pre-treatment
clinical and laboratory factors to identify patients at
risk of poor mobilization and to select the best therapeu-
tic approach shows conflicting results in the literature.
However, potentially more effective mobilization strate-
gies – such as chemo-mobilization and plerixafor-based
regimens should be considered for patients who have these
factors. A low number of CD34+ cells in peripheral blood
before apheresis is the most robust predictor of collection
failure; thus, the cell count should be performed in all
patients submitted to autologous transplantation of hema-
topoietic progenitor cells.
M
easurement
of
CD34+
cell
count
in
peripheral
blood
The use of flow cytometry for CD34 + cell count in
peripheral blood has become a standard technique to evalu-
ate the recruitment of these progenitor cells and to optimize
mobilization strategies,
3,4,7
having been implemented in
the routine practice in the vast majority of treatment cen-
ters.
35,36
Although several methodologies and cytometric
assays have been described, there can be great variability
among the observed cell counts and the lack of standard-
ized methods has led to the obtaining of widely differing
results.
35,37
The sample type and condition, the used reagent
and the characteristics of the employed anti-CD34 mono-
clonal antibodies are some potential error sources for the
cytofluorimetric measurement of CD34 + cell count.
38
The three main techniques of hematopoietic progeni-
tor cell count include the Milan/Mullhouse two-platform
protocol and the two-platform and single-platform analy-
sis systems of ISHAGE (International Society of Hema-
totherapy and Graft Engineering). In the two-platform
method, the percentage of CD34 + cells is determined
by flow cytometry and the leukocyte count is performed
in an automated hematology analyzer. The development
of single-platform methods allowed the absolute count of
CD34+ cells through a single device - the flow cytometer.
39
The results obtained with the three methods are apparently
comparable, with a low rate of divergence.
39,40
Given their
presumed interchangeability, the choice between these
three methods can be based on subjective criteria, such as
convenience, cost, and simplicity.
39
Recommendation: the exact quantification of CD4+
cells in peripheral blood is currently a highly relevant
factor for a successful autologous hematopoietic stem cell
transplantation. The purchase notices of kits for the analy-
sis of this parameter should be carefully prepared, aiming
at the acquisition of accurate, reliable products that have
been submitted to quality control testing.
M
obilization with
G-CSF
G-CSF is the most commonly used mobilizing
agent, either alone or in combination with chemotherapy.
The generally applied dose is 10 µg/kg subcutaneously,
with apheresis being started on the fifth or sixth day, until
the number of target cells is achieved.
41,42
Some studies
postulated that G-CSF dose division could result in bet-
ter mobilization. The pharmacological profile of G-CSF
demonstrates a maximum serum concentration within 2 to
8 hours after subcutaneous administration.
43
Considering an elimination half-life of 3 to 4 hours,
the dose division could result in higher basal serum
concentrations and, consequently, better mobilization.
44
However, studies comparing a single daily dose versus
divided dose of G-CSF showed conflicting results.
5,44
Higher doses of G-CSF (8 to 12 µg/kg/12h) resulted in
the collection of a higher number of CD34 + cells with
fewer apheresis procedures, suggesting the existence of a
dose-effect response.
45-47
The use of G-CSF has the advantage of allowing the
mobilization planning, resulting in more predictability,
A
nais
do
XX C
ongresso
B
rasileiro
da
S
ociedade
B
rasileira
de
T
ransplante
de
M
edula
Ó
ssea
| R
ev
. A
ssoc
. M
ed
. B
ra
. 2016; 62 (
suppl
. 1):10-15
11