Download Progenitor cell mobilization Good and poor CD34+ cells

Bone Marrow Transplantation (2004) 33, 1083–1087
& 2004 Nature Publishing Group All rights reserved 0268-3369/04 $25.00
www.nature.com/bmt
Progenitor cell mobilization
Good and poor CD34 þ cells mobilization in acute leukemia: analysis of
factors affecting the yield of progenitor cells
D Pastore, G Specchia, A Mestice, A Liso, A Pannunzio, P Carluccio, C Buquicchio, G Greco,
L Ciuffreda, G Pietrantuono and V Liso
Hematology Section, Department DIMIMP, University of Bari, Italy
Summary:
The factors possibly affecting the collection of peripheral
blood stem cells (PBSC) were evaluated in 104 de novo
acute leukemia patients (66 myeloid and 38 lymphoblastic
leukemias) in first cytological complete remission (CR); all
patients achieved CR after first-line induction chemotherapy. The acute myeloid leukemia patients (AML) were
given consolidation–mobilization chemotherapy with cytarabine, and daunoblastin or mitoxantrone or idarubicin; the
acute lymphoblastic leukemia patients (ALL) were given
consolidation–mobilization chemotherapy with cytarabine
and etoposide. In all patients, the collection of PBSC was
performed during recovery after giving consolidation
chemotherapy and granulocyte colony-stimulating factor
(G-CSF). Two main groups were considered according to
the CD34 þ cells 106/kg b.w. collected, that is, poor
mobilizers (PM), with a collection of o2 106/kg and
good mobilizers, with a collection of 42 106/kg. Of 104
patients, 27 (25.9%) were PM; 20/27 had AML and 7/27
had ALL. At multivariate analysis, a lower CD34 þ cells
count premobilization chemotherapy (CD34 steady state),
the presence of FUO (fever of unknown origin) or
infection, and a lower number of CD34 þ cells on the
first day of collection correlated with poor mobilization.
These results may enable early recognition of patients who
may have poor mobilization, and aid selection of patients
for different mobilization regimens.
Bone Marrow Transplantation (2004) 33, 1083–1087.
doi:10.1038/sj.bmt.1704437
Published online 12 April 2004
Keywords: acute leukemia; peripheral blood stem cell
mobilization
Peripheral blood stem cells (PBSC) are now widely used to
restore hematopoiesis following high-dose chemotherapy in
acute leukemia patients without an HLA-matched related
donor.1–4 Compared with autologous bone marrow, PBSC
Correspondence: Dr G Specchia, Hematology Section, Department
DIMIMP, University of Bari, Piazza Giulio Cesare 11, Bari 70124, Italy;
E-mail: [email protected]
Received 5 June 2003; accepted 13 November 2003
Published online 12 April 2004
transplants are associated with a shorter period of aplasia
and lower transplant-related mortality.5,6 PBSC are usually
collected by apheresis during the recovery phase following
chemotherapy plus granulocyte-colony-stimulating factor
(G-CSF). A significant correlation between sustained
hematologic engraftment and the quantity of reinfused
CD34 þ cells has been reported, indicating that collection
of CD34 þ cells is likely to be crucial for safe engraftment.7–10 The quantity of PBSC to be infused to achieve a
prompt recovery post transplant remains controversial, but
at least 2 106/kg CD34 þ cells are usually required in
autologous stem cell grafts to ensure hematopoietic
recovery after myeloablative chemotherapy.9–11 The number and type of premobilization chemotherapy or radiotherapy sessions, patient age and marrow involvement have
been reported to affect mobilization in lymphoma, myeloma and cancer patients.12–18 However, data regarding
PBSC collection in acute leukemia patients are limited.19–21
The purpose of this study was to identify CD34 cell
mobilization factors (diagnosis, age, sex, CD34 cell count
preconsolidation chemotherapy, type of chemotherapy,
infections or fever of unknown origin (FUO), CD34 þ
cells in the peripheral blood, white blood cells (WBC),
mononuclear cells (MNC) on the first day of collection) in a
series of 152 procedures performed on 104 de novo acute
leukemia patients who achieved cytological complete
remission (CR) after one cycle of chemotherapy.
Patients and methods
Patient population
From February 1990 to March 2002, 104 patients with de
novo acute leukemia in first cytological CR were eligible for
consolidation–mobilization chemotherapy plus G-CSF,
and underwent peripheral blood stem cell harvest; of these
patients (50 males and 54 females, aged 15–61 years,
median 40 years), 66 had acute myelogenous leukemia
(AML) and 38 had acute lymphoblastic leukemia (ALL).
The patient characteristics are listed in Table 1. The
patients had been treated with induction therapy according
to the GIMEMA protocols; the AML patients were treated
with cytarabine 100 mg/m2 by i.v. infusion over 24 h for 10
consecutive days, etoposide 100 mg/m2 once daily i.v. for 5
consecutive days and daunorubicin 50 mg/m2 (26 patients)
or mitoxantrone 12 mg/m2 (20 patients) or idarubicin
CD34 þ cells mobilization in acute leukemia
D Pastore et al
1084
Table 1
Clinical data of 104 patients undergoing mobilization procedures
AML
ALL
Number of patients
Sex (male/female)
Median age (years)
66
34/32
46 (16–59)
38
16/22
40 (14–58)
Induction chemotherapy (no. of patients)
DNR+E+ARA-C (26)
MITOX+E+ARA-C (20)
IDA+E+ARA-C (20)
VCR+DNR+PRD (38)
Consolidation-mobilization therapy (no. of patients)
DNR+ARA-C (26)
MITOX+ARA-C (20)
IDA+ARA-C (20)
E+ARA-C (38)
Interval from diagnosis to PBSC collection (days)
70 (58–85)
64 (60–72)
Interval from consolidation chemotherapy to PBSC collection (days)
18 (17–21)
14 (13–15)
E ¼ etoposide.
10 mg/m2 once daily (20 patients) for 3 consecutive days.
The ALL patients were treated with vincristine 1.4 mg/m2
i.v. weekly for 5 weeks, daunorubicin 30 mg/m2 once daily
for 3 days for three cycles overall, L-asparaginase 6000 UI/
m2 once daily subcutaneously for 10 days and prednisone
60 mg/m2 for 30 days. Before PBSC collection, all patients
had received one chemotherapy cycle as induction and one
consolidation–mobilization chemotherapy cycle. The day
before starting consolidation chemotherapy, the CD34 þ
peripheral blood cells count (CD34 steady state) was
determined.
PBSC mobilization
AML patients were mobilized with cytarabine 500 mg/m2
twice daily i.v. for 6 days and idarubicin 10 mg/m2 (20
patients) or mitoxantrone 12 mg/m2 (20 patients) or
daunorubicin 50 mg/m2 once daily i.v. for 3 days (26
patients). ALL patients (38) were mobilized with cytarabine
2 g/m2 i.v. twice daily for 2 days and etoposide (E) 150 mg/
m2 once daily i.v. for 3 days. In all patients, G-CSF was
administered subcutaneously at a dose of 5 mg/kg daily,
starting 10 days after the start of chemotherapy and
continuing until the day before the apheresis. PB CD34 þ
cell measurements were performed during the recovery
phase after chemotherapy when a white blood count of
42 109/l was reached. Immediately prior to PBSC
collection procedures, the PB with blood cell (WBC),
MNC and CD34 þ counts was determined and correlated
with the CD34 þ harvested.
PBCS were collected using blood cell separators
CS3000 þ (Baxter-Fenwal, Deerfield, IL, USA) using a
small-volume collection chamber; blood was collected via a
central venous access device (60 patients) or from
peripheral veins (44 patients), and a median of 8 l of blood
was processed per apheresis. In all, 48 patients underwent
one apheresis and 56 two apheresis procedures.
CD34 enumeration was performed on viable cells with a
dual-platform version of the ISHAGE protocol;22 briefly,
the WBC were measured with an automated hematology
analyzer and, if necessary, samples were diluted; 100 ml
Bone Marrow Transplantation
aliquots of the sample, containing between 5 106 and
10 106 cells, were incubated for 30 min at 41C with 10 ml of
phycoerythrin (PE)-conjugated anti-CD34 (HPCA-2), 10 ml
of fluorescein isothiocyanate (FITC)-conjugated anti-CD45
(2D1) (BD Biosciences) and 20 ml of 7-aminoactinomycin D
(final concentration 1 mg/ml). After incubation, the red cells
were lysed and cells were analyzed by fluorescenceactivated cell sorting (FACScan, Becton Dickinson) using
the CellQuest Software.
Statistical analysis
The clinical characteristics of the two groups of patients,
good mobilizers (GM) and poor mobilizers (PM), were
compared using two-tailed Fisher’s exact test for categorical variables and Student’s t-test or the Mann–Whitney
test for continuous variables. Pearson’s test was used to
correlate the CD34 steady state and CD34 at the first day of
apheresis with the number of CD34 þ cells collected. The
binary logistic regression model was used to analyse
parameters found to be statistically significant at univariate
analysis. Only P-values o0.05 were considered statistically
significant. All the statistical analyses were carried out
using the Statistical Package for Social Sciences (SPSS)
package, version 11.0 for Windows.
Results
Correlations between the number of PBSC collected and
patient diagnosis, sex, CD34 þ cells in the peripheral blood
premobilization chemotherapy (CD34 þ steady state),
chemotherapy, FUO or clinically or microbiologically
documented infection during the neutropenic phase after
consolidation chemotherapy, WBC, MNC and CD34 þ
blood cells at the first day of collections were determined by
multivariate analysis. According to the total collected
CD34 þ cells 106/kg b.w., two main groups were
considered that is, PM, with a collection of o2 106/kg
(27/104 pts, 25.9%), and GM, with a collection of
42 106/kg (77/104 pts, 74.1%) (Table 2). There was no
CD34 þ cells mobilization in acute leukemia
D Pastore et al
1085
Characteristics of 104 patients and outcome of mobilization
Patients
AML
ALL
Median age (years)
Sex M
Sex F
Median CD34+ steady-state 106/l (range)
Median WBC on the first day of collection 109/l (range)
Median MNC on the first day of collection 109/l (range)
AML treated with DNR (26)
AML treated with IDA (20)
AML treated with MITOX (20)
FUO or infection
PB CD34+ cells at the first day of collection 106/l (range)
Blood volume processed (l)
Number of apheresis procedures per patient
correlation between the diagnosis (AML vs ALL) and PM
or GM: 20/66 (30.3%) PM in AML vs 7/38 (18.4%) in ALL
(not significant). There was no statistically significant
correlation between the two groups regarding sex (22.2%
of females vs 20% of males were PM), age (median age 38
vs 46 years in GM and PM, respectively), WBC at the first
day of collection (7.8 109 vs 5.6 109/l in GM and PM,
respectively), MNC at the first day of collection (2.5 109
vs 1.8 109/l in GM and PM). In the GM group, 56
patients underwent one apheresis and 21 patients underwent two apheresis procedures; all 27 PM patients underwent two apheresis procedures. No large-volume
leukapheresis was done. The median of peripheral blood
processed was 10 and 15 l in GM and PM, respectively. No
significant differences in terms of PM were observed in
patients treated with DNR or MITOX or IDA (19.2% in
the DNR group vs 30% in the MITOX group vs 25% in the
IDA group were PM). The median percentage of CD34
premobilization chemotherapy was 0.08 (range 0.02–
0.19%) vs 0.02 (0.001–0.02%) in GM and PM, respectively;
this translated into a median concentration of 6 106/l
(range 4–10) vs 1 (range 0–5) in GM and PM, respectively
(Po0.05). A correlation analysis showed that steady-state
PB CD34 þ cells can reliably assess the CD34 þ cell yield
in mobilized PB (Po0.05; r ¼ 0.77) (Figure 1). When
grouped according to diagnosis, patients with ALL showed
a higher baseline CD34 þ cell count than AML patients
(7 vs 3 106/l in ALL and AML, respectively). In AML
patients, no differences were found between the two groups
(GM and PM), as regards the time from starting mobilization chemotherapy until apheresis (18 vs 19 days), the time
from starting mobilization chemotherapy until recovery of
neutrophils (17 vs 19 days) and the time between starting
induction therapy and starting mobilization chemotherapy
(48 vs 50 days); also, in ALL patients, no differences were
found between the two groups (GM and PM), as regards
the time from starting mobilization chemotherapy until
apheresis (14 vs 15 days), the time from starting mobilization chemotherapy until recovery of neutrophils (13 vs 15
days), and the time between starting induction therapy and
starting mobilization chemotherapy (48 vs 50 days). The
median number of CD34 þ cells at the first day of apheresis
Good mobilizers
Poor mobilizers
77 (74.1%)
46 (69.7%)
31 (81.6%)
38
38 (76%)
39 (78%)
6 (4–10)
7.8 (1.2–50)
2.5 (0.4–7.8)
21 (80.8%)
15 (75%)
14 (70%)
5/77 (6.4%)
160 (40–1200)
10 (8–12)
1.2
27 (25.9%)
20 (30.3%)
7 (18.4%)
46
12 (24%)
15 (28%)
1 (0–5)
5.6 (1.8–43)
1.8 (0.3–7)
5 (19.2%)
5 (25%)
6 (30%)
25/27 (92.5%)
12 (5–28)
15 (10–18)
2
Po0.05
Po0.005
Po0.001
45
Leukapheresis product CD34+ cells × 106/Kg
Table 2
40
35
30
25
20
15
10
5
0
0
2
4
6
8
10
Peripheral blood steady-state CD34+ × 10
12
6/L
Figure 1 Correlation of steady-state PB to mobilized CD34 þ cell counts
(r ¼ 0.77, Po0.05).
was also higher in GM vs PM (160 vs 12 106/l)
(Po0.001); the number of CD34 þ cells in the peripheral
blood on the first day of apheresis was strongly correlated
with the yields of CD34 in the relative harvest (r ¼ 0.81,
Po0.001) (Figure 2). A value below 20 106/l CD34 was
associated with an 85% probability of PM and a value
above 60 106/l CD34 was associated with a 90%
probability of GM. As regards FUO or clinically or
microbiologically documented infection during the neutropenic phase after consolidation chemotherapy, we found
that FUO or infection adversely affected mobilization (of
the patients with FUO or infection, 25/30 or 83.3% were
PM) (Po0.005). In the PM group with fever (25 patients),
there were 18 FUO and seven microbiologically documented infections; in the GM group with fever (five patients),
there were four FUO and one microbiologically documented infection.
Bone Marrow Transplantation
CD34 þ cells mobilization in acute leukemia
D Pastore et al
1086
CD34 cells collected (106/Kg)
60
50
40
30
20
10
0
0
200
400
600
800
1000
1200
1400
CD34 cell count (× 106/L) on the PB at the day of collection
CD34 þ cells collected kg, according to the CD34 þ cell
counts in the peripheral blood on the day of collection (r ¼ 0.81, Po0.001).
Figure 2
Discussion
There are few available data concerning mobilization of
PBSC in acute leukemia (AL) patients. We analyzed 152
PBSC collections in 104 AL patients in order to identify the
possible predictive factors of the CD34 þ cells collection;
all patients had received only one cycle of induction
chemotherapy and one cycle of consolidation–mobilization
chemotherapy. We have shown that, in the majority of
patients with AL (74.1%), a target quantity of 2 106/kg
could be collected from the peripheral blood following GCSF-supported consolidation chemotherapy; the threshold
number of 2 106 CD34 þ cells/kg was chosen on the basis
of previous studies demonstrating rapid and sustained
engraftment following reinfusion of this amount.7–11 When
consolidation–mobilization chemotherapy was started, the
patients were in first cytological CR following one cycle of
induction chemotherapy. The effect of patient age as a
predictor of the PBSC collection content is not clear. Lower
age was a significant factor in obtaining a larger number of
CD34 þ cells in the collection of patients in one study,7 but
age was not related to collection efficiency in other
studies;17,23 we did not find any correlation between sex
or age of the patients and the yields achieved. In terms of
diagnosis, 20/66 (30.3%) AML patients and 7/38 (18.4%)
ALL patients were poor mobilizers; the role of previous
stem cell damage from cytotoxic drugs is the likely
explanation,18,19,21,23 as these ALL patients had been less
heavily pretreated during induction chemotherapy than
AML patients. In our experience, patients with ALL
showed a higher baseline CD34 þ cell count preconsolidation chemotherapy than AML patients; this difference in
the yield of CD34 þ cells may be related to significant
differences in the hemopoietic reserve and individual
sensitivity of the hemopoietic progenitor cells to chemotherapy-related toxicity.17 Fruehauf et al 24 found that
PBSC counts in Hodgkin and non-Hodgkin lymphoma,
multiple myeloma and solid tumors during steady-state
hemopoiesis enable estimation of the yield of mobilized
Bone Marrow Transplantation
PBSC after G-CSF-supported cytotoxic chemotherapy. In
our experience in this group of 104 AL patients, a clear
correlation was observed between the steady-state PB
CD34 þ cell count and the outcome of mobilization; the
median number of CD34 premobilization chemotherapy
was higher in good than poor mobilizers (Po0.05). Highbaseline PB CD34 þ cells in AL patients predict a high
stem cell yield after mobilization with chemotherapy and
G-CSF, irrespective of diagnosis, age and type of chemotherapy. Other studies regarding lymphoma and solid
tumor patients25–27 reported a strong correlation between
the absolute cell number of circulating CD34 þ on the day
of apheresis and the number of CD34 þ cells collected; we
also found this correlation in our 104 AL patients
(Po0.001). In our report, the presence of clinically or
microbiologically documented fever or infection was
associated with poor mobilization (Po0.005); inflammatory cytokines with their negative effect on the proliferation
of stem cells may have a role in this poor mobilization.28–30
The number of prior cytotoxic chemotherapy cycles has
been reported to adversely affect the yield of PBSC in
lymphoma, myeloma and solid tumor patients,12–16 but
Jowitt et al 21 showed that the number of induction courses
received, and thus exposure to cytotoxic agents received,
made no significant difference to the subsequent CFU-GM
content in the peripheral blood in AL patients. In
our series, all patients had received only one line induction-chemotherapy and one consolidation–mobilization
chemotherapy before the PBSC collection. The timing
of PBSC collection is therefore crucial and should
be envisaged following efficient in vivo depletion of
leukemic cells, but still before the hemopoietic reserve is
impaired. We conclude that the CD34 cell count in the
steady state, the absence of fever or infection and
the CD34 þ cells in the peripheral blood on the day
of apheresis are reliable predictors of the success of
PBCS collection. High-baseline PB CD34 þ cells in AL
patients achieving CR after one chemotherapy cycle may
predict a high stem cell yield after the first consolidation
therapy and G-CSF. The routine determination of baseline
PB CD34 þ cell counts may identify patient groups at
risk of a poor stem cell yield, who would thus qualify
for enrolment in clinical trials on different mobilization
regimens.
Acknowledgements
This work was supported by Ministero dell’Istruzione dell’Università e della Ricerca (MIUR); we thank Ms MVC Pragnell,
BA, for language assistance in the preparation of the manuscript.
References
1 Gratwohl A, Passweg J, Baldomero H et al. Blood marrow
transplantation activity in Europe 1997: European Group for
Blood Marrow Transplantation (EBMT). Bone Marrow
Transplant 1999; 24: 231–245.
2 Korbling M, Fliedner TM, Holle R et al. Autologous blood
stem cell (ABSCT) versus purged bone marrow transplantation
CD34 þ cells mobilization in acute leukemia
D Pastore et al
1087
3
4
5
6
7
8
9
10
11
12
13
14
15
(pABMT) in standard risk AML: influence of source and cell
composition of the autograft on hematopoietic reconstitution
and disease free survival. Bone Marrow Transplant 1991; 7:
343–349.
Sanz MA, De la Rubia J, Sanz GF et al. Busulfan plus
cyclophosphamide followed by autologous blood stem cell
transplantation for patients with acute myeloblastic leukaemia
in first complete remission: a report from a single institution.
J Clin Oncol 1993; 11: 1661–1667.
De la Rubia J, Sanz JF, Martin G et al. Autologous blood
stem cell transplantation for acute myeloblastic leukaemia in
first complete remission: intensification therapy before transplantation does not prolong disease-free survival. Haematologica 1999; 84: 125–132.
To LB, Roberts MM, Haylock DN et al. Comparison of
haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell
transplant, autologous bone marrow transplant and allogeneic
bone marrow transplants. Bone Marrow Transplant 1992; 9:
277–284.
Beyer J, Schwella N, Zingsem J et al. Hematopoietic rescue
after high-dose chemotherapy using autologous peripheralblood stem cells or bone marrow: a randomised comparison.
J Clin Oncol 1995; 13: 1328–1335.
Besinger WI, Longin K, Appelbaum F et al. Peripheral blood
stem cells (PBSCs) collected after recombinant granulocyte
colony-stimulating factor (rhG-CSF): an analysis of factors
correlating with the time of engraftment after transplantation.
Br J Haematol 1994; 87: 825–831.
Weaver CH, Hazelton B, Birch R et al. An analysis of
engraftment kinetics as a function of the CD34 content of
peripheral blood stem cell collections in 692 patients after the
administration of myeloablative chemotherapy. Blood 1995;
86: 3961–3969.
Kiss JE, Rybka WB, Winkelstein A et al. Relationship of
CD34+ cell dose to early and late hematopoiesis following
autologous peripheral blood stem cell transplantation. Bone
Marrow Transplant 1997; 19: 303–310.
Haas R, Witt B, Mohle R et al. Sustained long-term
hematopoiesis after myeloablative therapy with peripheral
blood progenitor cell support. Blood 1995; 85: 3754–3761.
Ketterer N, Salles G, Raba M et al. High CD34(+) cell counts
decrease hematologic toxicity of autologous peripheral blood
progenitor cell transplantation. Blood 1998; 91: 3148–3155.
Alegre A, Tomas JF, Martinez-Chamorro C et al. Comparison
of peripheral blood progenitor cell mobilization in patients
with multiple myeloma: high dose cyclophosphamide plus
GM-CSF versus G-CSF alone. Bone Marrow Transplant 1997;
20: 211–217.
Besinger W, Appelbaum F, Rowley S et al. Factors that
influence collection and engraftment of autologous peripheral
blood stem cells. J Clin Oncol 1995; 13: 2547–2555.
Watts MJ, Sullivan AM, Jamieson E et al. Progenitor cell
mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor cell
quantity and quality and factors predictive for these parameters in 101 pre-treated patients with malignant lymphoma.
J Clin Oncol 1997; 15: 535–546.
Moskowitz CH, Glasmann GR, Wuest D et al. Factors
affecting mobilization of peripheral blood progenitor cells
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
in patients with lymphoma. Clin Cancer Res 1998; 4:
311–316.
Sautois B, Fraipont V, Baudoux E et al. Peripheral blood
progenitor cell collections in cancer patients: analysis of factors
affecting the yields. Haematologica 1999; 84: 342–349.
Dreger P, Kloss M, Petersen B et al. Autologous progenitor
cell transplantation: prior exposure to stem cell-toxic
drug determines yield and engraftment of peripheral blood
progenitor cell but not of bone marrow grafts. Blood 1995; 86:
3970–3978.
Kotasek D, Shepherd KM, Sage RE et al. Factors affecting
blood stem collections following high-dose cyclophosphamide
mobilization in lymphoma, myeloma and solid tumors. Bone
Marrow Transplant 1992; 9: 11–17.
Carral A, De La Rubia J, Martin G et al. Factors influencing
the collection of peripheral blood stem cells in patients with
acute myeloblastic leukemia and non-myeloid malignancies.
Leukaemia Res 2003; 27: 5–12.
Schelenk R, Dohner H, Pforsich M et al. Successful collection
of peripheral blood progenitor cells in patients with acute
myeloid leukaemia following early consolidation therapy with
granulocyte colony-stimulating factor-supported highdose cytarabine and mitoxantrone. Br J Haematol 1997; 99:
386–393.
Jowitt SN, Chang J, Morgenstern GR et al. Factors which
affect the CFU-GM content of the peripheral blood haemopoietic progenitor cell harvests in patients with acute myeloid
leukaemia. Br J Haematol 1998; 100: 668–694.
Moretti S, Dabusti M, Castagnari B et al. Comparison of
single and dual platform methodologies for the estimation
of CD34+ hematopoietic progenitor cells: correlation with
colony assay. Int J Biol Markers 2002; 17: 259–267.
Drake M, Ranaghan L, Morris M et al. Analysis of the effect
of prior therapy on progenitor cell yield: use of a chemotherapy scoring system. Br J Haematol 1997; 98: 745–749.
Fruehauf S, Schmitt K, Veldwijk R et al. Peripheral blood
progenitor cell (PBPC) counts during steady-state haemopoiesis enable the estimation of the yield of mobilized PBPC
after granulocyte colony-stimulating factor supported cytotoxic chemotherapy: an update on 100 patients. Br J Haematol
1999; 105: 786–794.
Diaz M, Sanchez-Garcia F, Lillo R et al. Large-volume
leukapheresis in pediatric patients: pre-apheresis peripheral
blood CD34+ cell count predicts progenitor cell yield.
Haematologica 1999; 84: 32–35.
Benjamin RJ, Linsley L, Fountain B et al. Preapheresis
peripheral blood CD34+ mononuclear cell counts as a
predictor of progenitor cell yield. Transfusion 1997; 37: 79–85.
Elliot C, Samsom DM, Armitage S et al. When to harvest
peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34positive concentration in peripheral blood. J Clin Oncol 1996;
14: 970–973.
Xiao W, Koizumi K, Nishio M et al. Tumor necrosis factoralpha inhibits generation of glycophorine A+ cells by CD34+
cells. Exp Hematol 2002; 30: 1238–1247.
Carlo-Stella C, Tabilio A. Stem cell and stem cell transplantation. Haematologica 1996; 81: 573–587.
Ogawa M. Differentiation and proliferation of hemopoietic
stem cells. Blood 1993; 81: 2844–2853.
Bone Marrow Transplantation