Symposium article
Annals of Oncology 14 (Supplement 1): i29–i36, 2003
DOI: 10.1093/annonc/mdg706
Impact of chemotherapy regimen and hematopoietic growth factor
on mobilization and collection of peripheral blood stem cells in
cancer patients
M. R. Nowrousian*, S. Waschke, P. Bojko, A. Welt, P. Schuett, P. Ebeling, M. Flasshove, T. Moritz,
J. Schuette & S. Seeber
Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School, Essen, Germany
Introduction
In cancer patients, peripheral blood stem cells (PBSC) are usually
mobilized by the application of chemotherapy and recombinant human granulocyte or granulocyte–macrophage colonystimulating factor (rhG-CSF and rhGM-CSF, respectively).
Among the chemotherapy regimens used, cyclophosphamide and
etoposide in intermediate to high doses (ID–HD), either as single
agent or in combination with other drugs, have been reported
to be particularly effective [1–22], as well as HD etoposide, even
*Correspondence to: Dr M. R. Nowrousian, Department of Internal
Medicine (Cancer Research), West German Cancer Center, University of
Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany.
Tel: +49-201-723-3127; Fax: +49-201-723-5984;
E-mail: [email protected]
Dedicated to Prof. Dr C. G. Schmidt on the occasion of his 80th birthday.
© 2003 European Society for Medical Oncology
in patients who have failed to mobilize PBSC with ID–HD
cyclophosphamide [18, 19, 21]. ID–HD cyclophosphamide or
etoposide, however, may be associated with substantial toxicities
[10, 12, 19, 23], and in some malignant diseases, cyclophosphamide or etoposide as single agents may not be the appropriate
treatment, even in ID–HD [24]. Conventional doses (CD) of
these drugs have been used in combination with other agents
[8, 25–42]. Another effective agent in mobilizing PBSC is ifosfamide, which is frequently used together with other drugs,
particularly etoposide [25–44]. Many regimens have been
reported to be useful in mobilizing PBSC [18, 21, 22, 33–40,
42–44], but there are a limited number of studies comparing the
efficacy of different drugs or drug combinations [4, 7, 8, 14, 16,
20, 25, 32]. In addition, there is no study comparing the efficacy
of the frequently used ID–HD cyclophosphamide, ifosfamide–
etoposide-based and CD cyclophosphamide regimens together
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Various chemotherapy regimens, combined with recombinant human granulocyte colony-stimulating factor
(rhG-CSF) or recombinant granulocyte–macrophage CSF (rhGM-CSF) are used in cancer patients to mobilize
and collect peripheral blood stem cells (PBSC). In this retrospective study, we evaluated and compared the
efficacy of such regimens in 262 patients with different types of malignant diseases. The following chemotherapy regimens were applied: ifosfamide–etoposide–cisplatin or bleomycin (n = 96; mainly patients with
testicular cancer); ifosfamide–etoposide plus or minus cytosine arabinoside (Ara-C) or vincristine (VCR)
(n = 52; mainly patients with lymphoma); cyclophosphamide–anthracycline (n = 53; mainly patients with
breast cancer); intermediate to high dose (ID–HD) cyclophosphamide (n = 37; mainly patients with breast or
ovarian cancer, or multiple myeloma; and others (n = 24). rhG-CSF or rhGM-CSF, each at an average daily
dose of 5 µg/kg body weight, were used in 166 and 96 patients, respectively. The study evaluated and compared the efficacy of these two cytokines. In patients receiving rhG-CSF, CD34+ cells could be collected
earlier (median: day 14 versus day 16) and there was a significantly higher white blood cell count (WBC)
(median 11 350 versus 5550/µl) and CD34+ cell count (median 88 versus 43/µl) at the start of apheresis, and a
significantly higher CD34+ cell yield (median 7.4 × 106 versus 4.6 × 106/kg) than in patients who received
rhGM-CSF. Among the various chemotherapeutic regimens used, each combined with rhG-CSF, ifosfamide–
etoposide plus or minus Ara-C or VCR mobilized a significantly higher number of CD34+ cells (median 119/µl)
and produced a significantly higher harvest of these cells (median 13 × 106/kg) than cyclophosphamide–
anthracycline (median 87/µl and 7 × 106/kg, respectively) or ID–HD cyclophosphamide (median 59/µl and
5 × 106/kg, respectively). Ifosfamide–etoposide plus or minus Ara-C or VCR was also superior to ifosfamide–
etoposide–cisplatin or bleomycin (median 78/µl and 9 × 106/kg, respectively), but at borderline significance.
The outcome of PBSC mobilization and collection appeared to be negatively influenced by the number of
relapses before the current salvage treatment. These data indicate that mobilization and collection of PBSC
strongly depend on the type of hematopoietic growth factor and chemotherapeutic regimen used. The data
further show rhG-CSF is a more effective growth factor than rhGM-CSF and ifosfamide–etoposide-based
regimens, particularly ifosfamide–etoposide plus or minus Ara-C or VCR, are highly effective regimens in
mobilizing and collecting CD34+ cells.
i30
phamide (n = 37; 14.1%), mainly in patients with breast cancer, ovarian cancer
or multiple myeloma; and other drug combinations (n = 24; 9.2%) (Tables
1 and 2). rhG-CSF (filgrastim; Amgen, Munich, Germany) or rhGM-CSF
(molgramostim; Essex, Munich, Germany), each at an average daily dose of
5 µg/kg body wt, were given subcutaneously as hematopoietic growth factor
in 166 and 96 patients, respectively. They were usually started 2–3 days after
the last chemotherapy dose and continued until completion of PBSC collection.
Stem cell monitoring and collection
Hematopoietic stem cells were determined as CD34+ cells using flow cytometry analysis carried out on a Coulter Epics XL (Coulter, Hialeah, FL, USA).
The cells were analyzed in a gate defined by CD45 antigen expression. Mouse
isotype control (IgG1*PE; Becton Dickinson, San Jose, CA, USA) was used
to account for unspecific fluorescence. To quantify the CD34+ cells, the
following fluorochrome-conjugated monoclonal antibodies were used:
CD34(Anti-HPCA-2)*PE (Becton Dickinson) and CD45(J33)*FITC (Immunotech, Marseille, France). About 1 × 106 cells were stained with the appropriate
amount of fluorochrome-conjugated antibody and incubated for 20 min at
4°C in the dark. Red blood cell lysis and leukocyte fixation were done with a
Coulter Q-Prep Workstation and the ImmunoPrep reagent system (Coulter).
Patients and treatment
From March 1993 to June 1997, 262 patients received chemotherapy and
rhG-CSF or rhGM-CSF to mobilize and collect PBSC (Tables 1 and 2). The
following chemotherapy regimens were used: ifosfamide and etoposide plus
cisplatin or bleomycin (n = 96; 36.6%), mainly in patients with germ cell
cancer; ifosfamide and etoposide with or without cytosine arabinoside or
vincristine (n = 52; 19.8%), mainly in patients with lymphoma; cyclophosphamide and doxorubicin or epirubicin (cyclophosphamide–anthracycline)
(n = 53; 20.2%), mainly in patients with breast cancer; ID–HD cyclophos-
Fifty thousand events were acquired for analysis. The total yield of each subset was calculated by multiplying the cell concentration with the collected
blood volume after each blood volume separated [11].
Daily CD34+ cell monitoring from patients’ peripheral blood samples was
started on day 10 after initiation of mobilization chemotherapy and PBSC
collection was carried out when the peak concentration of CD34+ cells was
expected to be reached, allowing the collection of a target number of ≥7.5 ×
106 CD34+ cells/kg body wt using a single apheresis. The target yield chosen
had the aim of supporting two cycles of high-dose chemotherapy, each with
at least 2.5 × 106 CD34+ cells/kg body wt, and to provide the same amount
of CD34+ cells as back-up.
Table 1. Patients
Malignancy
No. of
patients
Median age, years
(range)
Sex
(M/F)
Germ cell cancer
99
31 (15–53)
98/1
Hodgkin’s disease
16
34 (16–54)
11/5
Non-Hodgkin’s lymphoma
46
38 (17–62)
24/22
Breast cancer
70
41 (23–53)
0/70
Ovarian cancer
13
51 (20–63)
0/13
Multiple myeloma
18
53 (31–63)
7/11
262
36 (15–63)
140/122
Total
A Spectra blood cell separator (Gambro BCT, Lakewood, CO, USA) was
used to collect the stem cells. Blood was drawn and returned either via
peripheral veins or a double lumen Shaldon catheter. The patients’ blood
volume was calculated based on weight, height and gender. Anticoagulation
was done with citrate dextrose formula A (ACD-A; Baxter, Deerfield, IL,
USA) and heparin (Hoffmann-La Roche, Grenzach-Wyhlen, Germany). The
ACD-A to whole-blood ratio was set between 1:28 and 1:18, depending on the
patients’ platelet counts, and heparin was added at 6 U/ml ACD-A. Calcium
was replaced orally if symptoms of hypocalcemia occurred and platelet
transfusions were given if indicated to keep the platelet count ≥50 000/µl
at the start of apheresis. The whole-blood flow rate was set between 100 and
150 ml/min [11].
Table 2. Chemotherapy regimens and drug doses used to mobilize CD34+ cells
Regimen
Drug doses per cycle
Ifosfamide–etoposide–cisplatin or bleomycin
Ifosfamide 6000 mg/m2, etoposide 500 mg/m2,
cisplatin 100 mg/m2 or bleomycin 30 mg total
Ifosfamide–etoposide ± cytosine arabinoside (Ara-C)
or vincristine (VCR)
Ifosfamide 7500 mg/m2, etoposide 500–600 mg/m2,
Ara-C 500 mg/m2 or VCR 1 mg/m2
Cyclophosphamide–anthracycline
Cyclophosphamide 1200 mg/m2, doxorubicin 60 mg/m2
or epirubicin 90 mg/m2
Intermediate to high dose cyclophosphamide
Cyclophosphamide: 2000 mg/m2 in breast cancer;
2500 mg/m2 in ovarian cancer; 6000 mg/m2 in multiple
myeloma
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with an anthracycline. The aim of the present study was to make
such a comparison using the same apheresis technique and the
same target yield of PBSC.
Peripheral blood stem cells can be mobilized using rhGMCSF, rhG-CSF, chemotherapy alone or chemotherapy followed
by one of the two hematopoietic growth factors [45]. While rhGCSF as single agent has been reported to be superior to rhGMCSF [46, 47], the results of studies using chemotherapy and
rhG-CSF or rhGM-CSF are controversial [49–51]. In two studies,
rhG-CSF was found to mobilize significantly more PBSC than
rhGM-CSF [50, 51], but in another study, the two factors appeared
to have similar activity [49]. The present study therefore evaluated and compared the efficacy of these two cytokines. Further
aims of the study were to investigate additional factors that could
have an impact on mobilization and collection of PBSC and to
define pre-apheresis factors that could help to calculate the yield
of these cells and the amount of the blood volume that should be
processed to collect a particular target yield.
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Results
Predictive value of WBC and peripheral blood CD34+
cell count
To investigate the potential role of WBC count and peripheral
blood CD34+ cell count as predictive parameters for the yield of
CD34+ cells, both variables were correlated with the amount of
CD34+ cells collected from each microliter of blood on the first
day of apheresis. The latter was calculated by dividing the total
number of CD34+ cells collected by the total volume of the blood
processed. The aim of this approach was to establish a statistical
relationship that would allow one to predict the amount of
CD34+ cells that could be collected individually in each patient
at a certain WBC or CD34+ cell count in the peripheral blood and
the volume of the blood that should be processed in order to
collect a certain target amount of CD34+ cells/kg body wt. From
the two parameters evaluated, the concentration of CD34+ cells
in the peripheral blood showed a significant correlation
Comparison between rhG-CSF and rhGM-CSF
In patients receiving rhG-CSF, it was possible to collect CD34+
cells earlier and there was a significantly higher leukocyte and
CD34+ cell count in the peripheral blood at the start of apheresis
and a significantly higher CD34+ cell yield than in patients who
received rhGM-CSF (Table 4). Similar results were obtained
when the comparison was made in a homogenous group of
patients regarding sex, age, malignant disease and chemotherapy
regimen, such as patients with testicular cancer who exclusively
received the drug combination ifosfamide–etoposide–cisplatin
with rhG-CSF or rhGM-CSF (Table 4).
Comparison between chemotherapy regimens
In order to have comparable groups of patients regarding the use
of hematopoietic growth factor, the impact of chemotherapy on
CD34+ cell mobilization and collection was evaluated in patients
who received rhG-CSF. Among the chemotherapy regimens
applied, ifosfamide–etoposide plus or minus cytosine arabinoside
(Ara-C) or vincristine (VCR) mobilized a significantly higher
number of CD34+ cells and produced a significantly higher
harvest of these cells than cyclophosphamide–anthracycline
(Table 5) or ID–HD cyclophosphamide (Table 6). The cyclophos-
Table 3. Results of PBSC mobilization and collection on the first
day of apheresis in the entire group of 262 patients
Day of 1st PBSC collection
WBC at 1st PBSC collection (103/µl)
Median
Range
15
5–26
8.45
0.6–48.8
CD34+ cells/µl at 1st PBSC collection
70
7–5070
Processed blood volume (l)
17.3
3.2–33.2
CD34+ cells/µl blood processed
25
0.3–247
CD34+ cell collection efficacya
0.36
0.2–0.94
CD34+ cell yield (106/kg body wt)
6.7
0.02–1430
a
The ratio of CD34+ cells/µl blood processed to CD34+ cells/µl
blood.
PBSC, peripheral blood stem cell; WBC, white blood cell count.
Figure 1. Relationship between the absolute number of CD34+ cells/µl in
the peripheral blood on the first day of apheresis and the corresponding
amount of CD34+ cells collected. The median collection efficiency was
0.36, indicating that, for example, in a patient weighing 70 kg, 14.6 l blood
had to be processed to achieve a CD34+ cell harvest of 7.5 × 106 cells/kg
body wt at a CD34+ cell concentration of 100/µl in the peripheral blood
[(7.5 × 70):(100 × 0.36) = 14.6 l].
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For the entire group of patients, the median day of starting
CD34+ cell collection was day 15 after the beginning of chemotherapy. The median leukocyte and CD34+ cell counts in the
peripheral blood were 8.45 × 103/µl and 70/µl, respectively, on
the first day of apheresis and the median number of CD34+ cells
collected was 6.7 × 106 CD34+ cells/kg body wt. The median
volume of blood processed was 17.3 l, equal to a median of 4.1
times the patients’ blood volume (Table 3).
In 164 (62.6%) patients, only one apheresis was performed yielding a median of 10.6 × 106 CD34+ cells/kg body wt. In 71 (27.1%)
and 27 (10.3%) patients, one or two additional aphereses were
required to achieve an appropriate yield. The number of CD34+
cells harvested declined on day 2 and day 3 of apheresis, reaching a
median of 6.6 × 106/kg body wt and 7.0 × 106/kg body wt, respectively. For the complete apheresis, the median number of CD34+
cells collected was 8.2 × 106/kg body wt. The target yield of ≥7.5 × 106
CD34+ cells/kg body wt was achieved in 55.3% of patients reaching a median harvest of 13 × 106 CD34+ cells/kg body wt. The
median harvest was ≥5 × 106 CD34+ cells/kg body wt in 74.5% of
patients and ≥2.5 × 106 CD34+ cells/kg body wt in 89.7%.
(r = 0.817, P = 0.0001) with the yield of these cells (Figure 1).
The median collection efficiency, defined as the amount of
CD34+ cells collected from each microliter of blood, was 0.36
(Table 3) on the first day of apheresis, but declined to a median of
0.31 and 0.24 on the second and third day, respectively. No correlation was found between the leukocyte count in the peripheral
blood and the number of CD34+ cells collected (r = 0.08,
P = 0.20).
i32
Table 4. Comparison between rhG-CSF and rhGM-CSF in mobilizing and collecting PBSC
rhG-CSF
Day of 1st PBSC collection
3
rhGM-CSF
All patients (n = 166)
PEI (n = 20)
All patients (n = 96)
PEI (n = 71)
14a (9–26)
16 (13–20)
16 (5–23)
16 (5–23)
a
a
WBC at 1st PBSC collection (10 /µl)
11.4 (0.6–48.8)
10.0 (2.0–33.1)
CD34+ cells/µl at 1st PBSC collection
88a (10–5070)
78a (12–1525)
43 (7–774)
45 (10–774)
CD34+ cells/µl blood processed
30a (0.33–247)
30 (4–210)
16 (2.6–201)
17 (3–201)
7a (0.02–66)
9 (1–36)
6
CD34+ cell yield (10 /kg body wt)
5.6 (0.6–37.9)
4 (0.6–1430)
5.3 (0.6–37.9)
5 (1–50)
PEI, patients who received cisplatin, etoposide and ifosfamide (PEI); PBSC, peripheral blood stem cell; WBC, white blood cell count; rhG-CSF and rhGMCSF, recombinant human granulocyte and granulocyte–macrophage colony-stimulating factor, respectively. Data present median values and ranges.
a
Significant difference (P <0.05) in comparison with rhGM-CSF.
A (n = 50)
Day of 1st PBSC collection
14 (10–26)
3
WBC at 1st PBSC collection (10 /µl)
CD34+ cells/µl at 1st PBSC collection
5.9 (0.6–42)
119 (11–1442)
B (n = 49)
P
13 (11–16)
0.0001
16.3 (4–48.8)
0.0001
87(14–579)
0.027
CD34+ cells/µl blood processed
48 (0.33–247)
31 (4–118)
0.058
CD34+ cell yield (106/kg body wt)
13 (0.02–66)
7(1–24)
0.023
Ara-C, cytosine arabinoside; PBSC, peripheral blood stem cell; rhG-CSF, recombinant human
granulocyte colony-stimulating factor; VCR, vincristine; WBC, white blood cell count. Data
present median values and ranges.
phamide–anthracycline regimen, on the other hand, appeared
to be superior to ID–HD cyclophosphamide [6] (Table 7). There
was also a difference between the two groups of ifosfamide–
etoposide-based regimens, favoring ifosfamide–etoposide plus
or minus Ara-C or VCR over ifosfamide–etoposide–cisplatin,
but at borderline significance (Table 8).
Logistic regression analysis
The impact of hematopoietic growth factor and chemotherapy
regimen, as well as that of age (≤40 versus >40 years), sex, type
of malignancy, pretreatment (yes versus no) and the number of
relapses (0–5) on the mobilization and collection of CD34+ cells
was tested in a logistic regression analysis, including the yield of
at least 7.5 × 106 CD34+ cells as the target. In this analysis, in
accordance with the data presented above, the use of ifosfamide–
etoposide-based regimens or other drug combinations and the
use of rhG-CSF or rhGM-CSF independently and significantly
(P = 0.001 and P = 0.030, respectively) influenced the harvest
of CD34+ cells. Another significant factor was the number of
relapses the patients had before receiving the current salvage
treatment (P = 0.011).
Discussion
In accordance with other studies [52–54], our results show a high
predictive value of CD34+ cell concentration in the peripheral
blood and the yield of these cells in the apheresis product. The
number of CD34+ cells collected increased with their increasing
level in the peripheral blood, but the collecting efficiency,
defined as the proportion of cells that could be collected from
each microliter of blood, decreased from a median of 0.36 on the
first day of apheresis to a median of 0.31 and 0.24 on the second
and third day, respectively. Using such collection efficiency
values and the following formula, it is possible to calculate
roughly the expected yield of CD34+ cells at a certain concentration of these cells in the PB and to calculate the volume of the
blood that should be processed in order to obtain a certain target
amount of CD34+ cells/kg body wt (Figure 1): [target yield of
CD34+ cells (106) × body wt (kg)] : [CD34+ cell count in the
peripheral blood (µl) × collection efficiency] = blood volume to
be processed (l). The collection efficiency of CD34+ cells, however, may differ considerably in each patient from the median
value, probably related to variations in apheresis technique and
individually varying drop of CD34+ cell count and additional
CD34+ cell mobilization during CD34+ cell harvest [55, 56].
ID–HD cyclophosphamide is frequently used to mobilize and
collect PBSC [1, 3, 5, 9, 10, 12–14, 16, 17, 32]. Other frequently
used regimens are ifosfamide–etoposide-based regimens [25–28,
30–35, 37–42] and combinations of CD cyclophosphamide with
various drugs, such as anthracyclines [8, 25]. It is therefore of
particular interest to evaluate and compare the efficacy of these
regimens to define the impact of the type of chemotherapy on the
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Table 5. PBSC mobilization and collection in patients receiving rhG-CSF and ifosfamide–
etoposide ± Ara-C or VCR (A) or cyclophosphamide–anthracycline (B)
i33
Table 6. PBSC mobilization and collection in patients receiving rhG-CSF
and ifosfamide–etoposide ± Ara-C or VCR (A) or ID–HD
cyclophosphamide (B)
A (n = 50)
Day of 1st PBSC collection
WBC at 1st PBSC collection
(103/µl)
CD34+ cells/µl
at 1st PBSC collection
14 (10–26)
5.9 (0.6–42)
119 (11–1442)
CD34+ cells/µl
blood processed
48 (0.33–247)
CD34+ cell yield
(106/kg body wt)
13 (0.02–66)
Table 8. PBSC mobilization and collection in patients receiving rhG-CSF
and ifosfamide–etoposide–cisplatin (A) or ifosfamide–etoposide ± Ara-C
or VCR (B)
B (n = 29)
P
13 (10–21)
0.081
Day of 1st PBSC collection
13.9 (2.9–48.8)
0.0001
WBC at 1st PBSC collection 10 (2–33.1)
(103/µl)
59 (10–459)
0.0001
CD34+ cells/µl
at 1st PBSC collection
78 (12–1525)
21 (2–161)
0.001
CD34+ cells/ml
blood processed
30 (4–210)
5 (0.6–45)
0.001
CD34+ cell yield
(106/kg body wt)
A (n = 20)
16 (13–20)
9 (0.76–36)
B (n = 50)
14 (10–26)
P
0.0001
5.9 (0.6–42)
0.046
119 (11–1442)
0.059
48 (0.33–247)
0.065
13 (0.02–66)
0.054
Ara-C, cytosine arabinoside; PBSC, peripheral blood stem cell; rhG-CSF,
recombinant human granulocyte colony-stimulating factor; VCR,
vincristine; WBC, white blood cell count. Data present median values and
ranges.
Table 7. PBSC mobilization and collection in patients receiving rhG-CSF
and ID–HD cyclophosphamide (A) or CD cyclophosphamide–
anthracycline (B)
rhabdomyosarcoma, since, beside their efficacy in mobilizing
PBSC, they represent highly effective treatments of these diseases [27, 28, 32–37, 39–42, 57, 58]. Such regimens have also
been used for mobilizing PBSC in patients with chronic myelogenous leukemia and multiple myeloma [30, 31, 38, 59].
Another important factor determining the yield of PBSC found
in our study was the number of relapses that the patients had
before they received the current salvage chemotherapy to mobilize CD34+ cells. This finding confirms the results of other
studies indicating a negative relationship between the intensity of
cytotoxic pre-treatments, particularly prolonged application of
alkylating agents, and the outcome of CD34+ cell mobilization
and collection [3, 5, 13, 15, 17, 60–63]. PBSC harvest should,
therefore, be planned as early as possible in the course of disease
of patients who are candidates for autologous PBSC transplantation.
As a single agent, rhG-CSF has been shown to mobilize more
CD34+ cells than rhGM-CSF [46–48]. In combination with chemotherapy, however, there are controversial results regarding the
potential of the two factors in mobilizing CD34+ cells. While in a
small randomized study, the two growth factors showed similar
activity [49] in two other randomized studies, including a study
with a large number of patients, rhG-CSF appeared to be superior
to rhGM-CSF in mobilizing CD34+ cells [50, 51] and, additionally, in reducing the toxicities of chemotherapy [51]. Our study
similarly shows a significant difference between the two growth
factors, favoring rhG-CSF. This difference was also evident
when the effects of rhG-CSF and rhGM-CSF were compared in a
homogenous group of patients with regard to age, gender and
chemotherapy regimen. In addition, the type of growth factors
used was found to be of independent significance for mobilizing
CD34+ cells and achieving the target yield of these cells in logistic regression analysis.
In conclusion, the results of the present study show a significant impact of the type of chemotherapy and hematopoietic
growth factor on mobilization and yield of PBSC. The results
further indicate rhG-CSF as a factor with a greater potential of
Day of 1st PBSC collection
A (n = 29)
B (n = 49)
P
13 (10–21)
13 (11–16)
0.379
WBC at 1st PBSC collection 13.9 (2.9–48.8)
(103/µl)
16.3 (4–48.8)
0.492
CD34+ cells/µl
at 1st PBSC collection
59 (10–459)
87 (14–579)
0.025
CD34+ cells/µl
blood processed
21 (2–161)
31 (4–118)
0.018
7.3 (1–24)
0.040
CD34+ cell yield
(106/kg body wt)
4.8 (0.6–45)
CD, conventional-dose; ID–HD, intermediate to high dose; PBSC,
peripheral blood stem cell; rhG-CSF, recombinant human granulocyte
colony-stimulating factor; WBC, white blood cell count. Data present
median values and ranges.
outcome of PBSC mobilization and collection. The results of our
study clearly show a strong relationship between the chemotherapy regimen used and the amount of CD34+ cells that can be
collected. Such a relationship has also been observed in some
other studies comparing the efficacy of various chemotherapy
regimens [8, 13, 16, 25, 32]. In one study, the combination of
ifosfamide, etoposide and epirubicin was found to be superior to
ID cyclophosphamide [32], and in another study, the addition of
etoposide to ID cyclophosphamide improved the results of PBSC
mobilization and collection [13]. In our study, ifosfamide–etoposide-based regimens, particularly those containing ifosfamide
plus etoposide alone or with Ara-C or VCR, appeared to be
significantly more effective than ID–HD cyclophosphamide or a
combination of CD cyclophosphamide and an anthracycline.
Ifosfamide–etoposide-based regimens are frequently used in
patients with malignant lymphoma, testicular cancer, lung cancer
and other solid tumors, such as Ewing’s sarcoma and alveolar
Downloaded from http://annonc.oxfordjournals.org/ at Pennsylvania State University on March 3, 2014
Ara-C, cytosine arabinoside; ID–HD, intermediate to high dose; PBSC,
peripheral blood stem cell; rhG-CSF, recombinant human granulocyte
colony-stimulating factor; VCR, vincristine; WBC, white blood cell count.
Data present median values and ranges.
i34
mobilizing CD34+ cells than rhGM-CSF. Among the chemotherapy regimens evaluated, ifosfamide–etoposide-based regimens, particularly ifosfamide plus etoposide alone or with Ara-C
or VCR, appear to be more effective than ID–HD cyclophosphamide or CD cyclophosphamide combined with an anthracycline. Independent of the chemotherapy regimens and growth
factors used, the yield of CD34+ cells seems to be significantly
influenced by the number of relapses that the patients have
suffered in the course of their disease.
11.
12.
13.
Disclosure
14.
References
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