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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 455-464
Peripheral Blood Stem Cell Transplantation From Unrelated Donors: A
Comparison With Marrow Transplantation
By
O. Ringdén,
M. Remberger,
V. Runde,
M. Bornhäuser,
I.W. Blau,
N. Basara,
K. Hölig,
D.W. Beelen,
H. Hägglund,
O. Basu,
G. Ehninger, and
A.A. Fauser
From the Center for Allogeneic Stem Cell Transplantation and
Department of Clinical Immunology, Huddinge Hospital, Huddinge, Sweden;
the Clinic for Bone Marrow Transplantation and Department of Pediatric
Hematology and Oncology, University Clinic Essen, Essen, Germany; the
Department of Hematology, Dresden, Germany; and the Clinic of BMT,
Hematology and Oncology, Idar-Oberstein, Germany.
 |
ABSTRACT |
Peripheral blood stem cell (PBSC) transplants from HLA-A, -B, and
-DR compatible unrelated donors (n = 45) were compared with bone
marrow (BM; BM group, n = 45). Eighteen patients received CD34-selected PBSC (CD34 group). The PBSCs contained more mononuclear cells, CD34+, CD3+, and CD56+
cells compared with marrow (P < .001). Engraftment was
achieved in all 45 patients in the BM group, in 43 of 45 (95%) in the
PBSC group, and in 14 of 18 (78%) in the CD34 group (P < .01). In multivariate analysis, a short time to absolute neutrophil
count (ANC) equal to 0.5 × 109/L was associated with the
PBSC/CD34 groups (P < .001) and granulocyte colony-stimulating factor (G-CSF) treatment (P = .017). A short time to platelets equal to 50 × 109/L was
associated with PBSC (P = .003) and no methotrexate
(P = .015). Grades II-IV acute graft-versus-host disease
(GVHD) was 20% in the BM controls, 30% in the PBSC group, and 18% in
the CD34 group (not significant [NS]). The probability of chronic GVHD was 85% in the BM group, 59% in the PBSC group, and 0% in the
CD34 group (P < .01). One-year transplant-related mortality was 21% and 27% and survival was 53% and 54% in the BM and PBSC groups, respectively (NS). The 2-year relapse-free survival was 41%
and 46% in the two groups, respectively.
© 1999 by The American Society of Hematology.
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INTRODUCTION |
PERIPHERAL BLOOD stem cells (PBSC) from
HLA-identical siblings are increasingly used as an alternative source
of hematopoietic stem cells to bone marrow (BM).1-10 In
1995, approximately 500 PBSC from HLA-identical siblings were reported
to the European Group for Blood and Marrow Transplantation (EBMT); in
1996, the figure increased to more than 1,000.10 In
contrast to PBSC from HLA-identical siblings, only a few patients have
been reported who received PBSC from unrelated donors.11-14
There have been several reasons for the reluctance to use PBSC from
unrelated donors. One concern has been the ethics of using unrelated
donors to mobilize PBSC, although the side-effects after the
administration of granulocyte colony-stimulating factor (G-CSF) to
normal donors are tolerable after several years of
follow-up.15 Another concern has been that the high T-cell
content of PBSC would increase the risk of graft-versus-host disease
(GVHD).11,13,16 We report here the experience of PBSC from
unrelated donors at four European Bone Marrow Transplant Units.
| |
PATIENTS AND METHODS |
Patients.
The patients were eligible for transplant with PBSC if they had a
disease for which marrow transplantation was indicated and after
approved informed consent was obtained from the donor and recipient. In
all, 63 patients received PBSC as an alternative to BM.
Transplantations were performed between February 1993 and September
1998. Patients receiving PBSC were divided into two groups: those
receiving unmanipulated grafts (PBSC group, n = 45) and those receiving
CD34+-selected cells (CD34 group, n = 18). Among the PBSC
patients, 17 were from Dresden (all CD34 selected), 16 were from Essen, 16 were from Huddinge, and 14 were from Idar-Oberstein (1 CD34 selected). Patients' and donors' characteristics are given in Table 1.
Informed consent.
Patients and donors were asked to participate in a study evaluating
transplantation with PBSC as an alternative to BM. All patients and
donors gave informed consent approved by the institutional review board
at each center and also approved by the Ethics Committee at Huddinge
Hospital and the Universities of Essen, Dresden, and Idar-Oberstein.
BM control group.
A control group of 45 patients who received BM from unrelated donors
was selected. Each patient who received an unrelated PBSC was matched
with a patient who received BM. As many variables as possible were
matched between the control receiving BM and the patient receiving
unmanipulated PBSC. The following prognostic factors were matched: HLA
compatibility, diagnosis, disease stage, age (less than or greater than
20 years of age), GVHD prophylaxis, and transplant center. The patient
transplanted with BM closest in time to each PBSC patient was selected.
Among the controls, 15 were from Essen, 16 were from Huddinge, and 14 were from Idar-Oberstein. Various characteristics of the controls are
given in Table 1.
Donors.
All donors were HLA-A and -B compatible with the recipient. All
donor-recipient pairs were in addition DRB1 compatible, except for 2. In these 2 patients, a DRB1 subtype mismatch was present. One recipient
was DRB1 1303 and the donor was 1302. The other recipient was 0408 and
the donor was 0404. Both patients received PBSC in Essen. DRB3 typing
was not performed in all patients. HLA-typing was serological for class
I and polymerase chain reaction-single-stranded polymorphism
(PCR-SSP) for class II.17 All PBSC donors
received G-CSF (Rhône-Poulenc Rorer [Lyon, France] or
Amgen-Roche Inc [Thousand Oaks, CA]). The G-CSF dose ranged from 9 to
12.5 µg/kg/d, administered subcutaneously once daily. G-CSF was
administered for 4 days to 14, for 5 days to 42, and for 6 days to 7 donors. Among the donors producing unmanipulated PBSC, one
leukapheresis was performed in 29 cases and two leukaphereses in 16. Among the donors providing CD34-selected cells, two leukaphereses were
performed in 17 patients and one leukapheresis was performed in 1 patient. The donors complained of skeletal pain from G-CSF, which was
relieved by paracetamol, but no other adverse effects were reported.
CD34 selection.
The apheresis products were T-cell depleted by positive selection of
CD34+ cells, using immunomagnetic beads (Isolex 300 SA;
Baxter, Deerfield, IL).18
Treatment regimens.
Conditioning and immunosuppression are shown in
Table 2. Detailed descriptions of the
myeloablative therapy, immunosuppression, and patient care at the
different centers have been reported elsewhere.18-20 Most
patients receiving BM or PBSC were conditioned with cyclophosphamide (CY) at 60 mg/kg/d, administered for 2 consecutive days, combined with
total body irradiation (TBI) at a dose ranging from 10 to 13.5 Gy. All
patients receiving CD34-selected PBSC were treated with busulfan (BU)
at 16 mg/kg administered over 4 days, combined with CY at 200 mg/kg in
17 patients and at 120 mg/kg in 1 patient. As additional pretransplant
immunosuppression, antithymocyte globulin (ATG) or OKT-3 was
administered to all patients in the CD34 group and to some of the other
patients (Table 2). Among the recipients of BM or unmanipulated PBSC,
cyclosporine (CsA), combined with a short course of methotrexate, was
the commonest regimen.21
Evaluation and definition.
Determinations of CD34+, CD3+, and
CD56+ cells were performed on unseparated BM or
leukapheresis product by flow cytometry, as previously
described.14 Neutrophil engraftment was defined as occurring on the first of 2 consecutive days, with an absolute neutrophil count (ANC) greater than 0.5 × 109/L.
Platelet engraftment was defined as on the first day of a platelet
count greater than 50 × 109/L without platelet
transfusions. Acute GVHD was graded according to standard
criteria.22 Bacteremia was defined as the first positive
blood culture related to a febrile episode during the first month after
transplantation. Chronic GVHD was assessed in patients alive after day
90.23 Cytomegalovirus (CMV) reactivation was
determined with PCR.24 In addition, patients in
Idar-Oberstein and Essen were followed weekly by the pp 65 antigen in
blood leukocytes. Transplant-related mortality (TRM) was defined as
death with no relapse. Relapse was diagnosed on BM specimens taken at
regular intervals and when clinically indicated.
Statistics.
Analysis was performed on October 9, 1998, with a median follow-up of
12 months (range, 1 to 37 months). The Mann-Whitney U-test was used to
compare cell yield, time to engraftment, transfusions, and
hospitalization. The probability of GVHD, TRM, relapse, leukemia-free survival (LFS), and survival were compared using the method of Kaplan-Meyer with a log-rank test (Mantel-Haenszel).25
Cox's regression model was used for multivariate
analysis.26 Factors with P = .1 in the univariate
analysis were included in the multivariate analysis. The following
factors were analyzed: methotrexate, cell dose, CD34 dose, CD3 dose,
G-CSF posttransplant, BM group, PBSC group, CD34 group, age, disease,
and disease stage. For TRM, relapse, and survival, GVHD was also
included. Only patients surviving more than 30 days were included in
the analysis of acute GVHD. A minimum of 90 days of follow-up was the
criterion for chronic GVHD.
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RESULTS |
Cell yield in grafts.
Nucleated cells (NC), CD34+, CD3+, and
CD56+ cells were significantly higher in the PBSC
leukapheresis product than in the BM control grafts
(Table 3, P < .001).
The CD3+ and CD56+ cell contents in PBSC were
more than 10-fold higher than in BM. The CD34 cell-selected grafts
contained the same number of CD34+ cells as the BM grafts.
The contents of NC, CD3+, and CD56+ cells were
significantly lower in the CD34 group than in the other two groups.
Patients in the CD34 group received a median of 1.8 × 105 CD3+ cells/kg.
Engraftment, transfusions, and hospitalization.
Engraftment (ANC >0.5 × 109/L) occurred in all
patients in the BM group, in 43 of 45 (95%) in the PBSC group, and in
14 of 18 (78%) in the CD34 group (P < .01 v BM).
However, one later graft failure occurred in the BM controls. Time to
ANC greater than 0.5 × 109/L was significantly faster
in the PBSC than in the BM group (Table 4,
P < .001, Fig 1). Time to reach
a platelet count greater than 50 × 109/L, without
platelet transfusions, also was longer in the patients receiving BM
than in the other two groups (P < .01). The CD34 group
required fewer platelet transfusions than the BM group (P = .014). No other difference in the number of transfusions was detected
between the three groups. The median time of discharge from hospital
was on day 38 after transplantations in all groups.
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| Fig 1.
Days to and ANC recovery to greater than 0.5 × 109/L after stem cell transplantation (SCT) with
unmanipulated PBSC, BM, or CD34-selected peripheral blood stem cells
(CD34). PBSC group versus BM group, P < .001. BM versus CD34
group, P = .08.
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In the univariate analysis, the following factors were associated with
a faster ANC greater than 0.5 × 109/L: cell dose
(P = .005), CD34 dose (P = .02), G-CSF posttransplant (P = .016), PBSC or CD34 group versus BM group (P < .001), and PBSC group versus others (P = .005). In the
multivariate analysis, PBSC and CD34 groups versus BM group and G-CSF
treatment were associated with a shorter time to ANC equal to 0.5 × 109/L (Table 5). Short
time to a platelet count equal to 50 × 109/L was
associated with PBSC and CD34 group versus BM group (P = .005)
and PBSC group versus the other two groups (P = .02) in univariate analysis. In the multivariate analysis, the PBSC group and
no methotrexate were significant (Table 5).
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Table 5.
Multivariate Analysis of Factors for Time to  0.5 × 109 ANC/L, Platelets 50 × 109/L, TRM,
Acute GVHD, Relapse, Survival, and LFS
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Infections.
Bacteremia occurred during the first 30 days in 49% of the patients
receiving BM, in 38% in the PBSC group, and in 11% of those receiving
CD34-enriched cells. In the BM group, 18 patients had a positive
coagulase-negative staphylococcal infection, compared with 10 in the
PBSC group. Bacteremia caused by  -streptococci, occurred in 3 and 2 patients in the two groups, respectively. Other types of septicemia
were seen in 1 patient in the BM group, in 5 in the PBSC group, and in
2 in the CD34 group. A positive CMV PCR was found in 13 patients in the
BM group, in 16 in the PBSC group, and in 4 in the CD34 group. CMV
interstitial pneumonitis occurred in 1 each of the first two groups and
in 2 in the CD34 group. In the latter group, 2 also had had CMV hepatitis.
One patient each in the three groups had Aspergillus infection. Two
patients in the PBSC group had invasive Candida infections.
Acute and chronic GVHD.
The incidence and grading of acute GVHD in the various groups are shown
in Table 4. The cumulative incidence of acute GVHD grades II-IV did not
differ significantly between the three groups (Fig 2). The cumulative incidences in
grades III-IV acute GVHD were 16% in the BM group, 14% in the PBSC
group, and 6% in the CD34 group. In the CD34 grafts, the number of
CD3+ cells given to patients with grades 0-I acute GVHD was
a median of 1.8 × 105/kg (range, 0.2 to 3.9 × 105/kg) versus 1.8 × 105/kg (range, 0.9 to 3.2 × 105/kg) in those with grades II-IV. In
multivariate analysis, acute GVHD grades II-IV was associated with OKT3
treatment, age greater than the median (30 years), and donor CMV
seropositivity (Table 5). The number of patients with chronic GVHD is
also shown in Table 4. No patient in the CD34 group developed chronic
GVHD, which was significant versus the BM group (P < .001)
and the PBSC group (P = .004). The 1-year cumulative incidence
of chronic GVHD in the BM group was 77%, compared with 65% in the
PBSC group (Fig 3).
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| Fig 2.
Time to and cumulative incidence of grades II-IV acute
GVHD after stem cell transplantation (SCT) of unrelated PBSC (30%), BM
(20%), or CD34 selected PBSC (CD34; 18%).
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| Fig 3.
Time to and cumulative incidence of chronic GVHD in
recipients of BM (85%) or PBSC (59%; P = .4).
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Causes of death, relapse, and survival.
Causes of death are shown in Table 6.
Overall TRM and patient survival rates did not differ significantly
between the three groups (Figs 4 and
5). The 1-year survival rates were 53% in
the BM group and 54% in the PBSC group. At 2 years, the actuarial survival rates were 45% in the BM group versus 50% in the PBSC group.
In patients with hematological malignancies, the probability of relapse
did not differ significantly between the two groups (Fig 6). At 1 year, the probabilities of
relapse were 38% in the BM controls and 34% in the PBSC patients. For
early disease, relapse probability was 14% in both groups. In
high-risk patients, the corresponding figures for the BM group was
74%, compared with 53% for the PBSC group (not significant [NS]).
Relapse-free survival rates did not differ significantly between the
two groups (Fig 7). One year after
transplantation, relapse-free survival rates were 48% in the BM
controls and 46% in the PBSC group. In patients with low-risk disease,
LFS at 1 year was 63% in the PBSC group and 70% in the BM group. In
patients with high-risk disease, the corresponding figures were 33%
and 31% in the two groups, respectively.
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| Fig 6.
Time to and cumulative incidence of relapse in patients
with hematological malignancies and those receiving BM or unmanipulated
PBSC from unrelated donors.
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| Fig 7.
Relapse-free survival (RFS) of patients grafted with
unmanipulated PBSC or BM from unrelated donors.
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At 1 year, the CD34 group had a TRM of 60%, a survival rate of 31%, a
relapse rate of 48%, and an LFS of 25%. The Kaplan-Meier curves did
not differ significantly from the other two groups.
Multivariate analysis for TRM, relapse, and survival.
For TRM, the following risk-factors were significant in multivariate
analysis, no methotrexate, and acute GVHD grades II-IV (Table 5).
Relapse was associated with high risk disease and absence of chronic
GVHD in multivariate analysis. The following factors were significant
in the multivariate analysis of survival: low-risk disease, chronic
myeloid leukemia (CML) versus acute leukemia, age less
than 35 years, and acute GVHD grades 0-I. For LFS, low-risk disease and
chronic GVHD were significant in the multivariate analysis.
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DISCUSSION |
This study shows that PBSC from unrelated HLA-A, -B, -DR compatible
donors can be safely administered as an alternative to BM. The PBSC
group had a significantly faster engraftment of ANC and platelets than
that in the BM controls. This is in agreement with several studies
comparing PBSC with BM from HLA-identical siblings and is also in line
with the preliminary experience using PBSC from unrelated
donors.4-6,13 The vast majority of patients in the BM and
PBSC groups were treated with GVHD prophylaxis, including methotrexate,
which prolongs engraftment more than cyclosporine used
alone.27 G-CSF posttransplant, which enhances engraftment, was also administered to similar percentages of patients in the BM and
PBSC groups. Patients in the BM group received G-CSF for a longer time
(Table 2). However, a randomized trial in recipients of unrelated BM
showed no difference in time to ANC, if G-CSF was started at 0, 5, or
10 days after transplantation.28 The reason for the faster
engraftment in the PBSC patient than in those receiving BM is probably
because of the higher graft content of CD34+ cells. For
engraftment of ANC and platelets, the CD34 content of the graft appears
to be of utmost importance.14,29 Therefore, it may seem
surprising that the patients receiving CD34-selected cells had as fast
an engraftment as those receiving PBSC, despite fewer CD34 cells in the
graft (Tables 4 and 5). The reason for this is probably that only one
third of the patients receiving CD34-selected cells received
methotrexate posttransplant (Table 2). In a randomized trial by the
EBMT, there was no difference in time to ANC and platelet engraftment
in HLA-identical siblings receiving PBSC as compared with
BM.10 This is probably because the CD34 contents were the
same in the two groups. However, despite the faster engraftment in the
PBSC and CD34 groups, time to discharge from hospital did not differ
from the BM group (Table 4). The reason for this may be that there are
several other problems, such as infections, nutrition, and GVHD, that
must be dealt with before the patients can be discharged. Moreover,
PBSC from unrelated donors is a new procedure and, because of lack of
experience, at least in the beginning, discharge may have been delayed
in some patients.
Graft failure was more common in the CD34 group than in recipients of
unmanipulated grafts in this study (P < .01). This is in
accordance with the experience that T-cell depletion increases the risk
of graft failure.30,31
An important finding is that there was no difference in acute GVHD
between patients receiving PBSC compared with those receiving BM,
despite the 10-fold higher content of T cells (Table
3).13,16 In HLA-identical siblings, we found no correlation
between T-cell dose in T-replete BM grafts and the probability of
moderate-to-severe acute GVHD, which is in agreement with
this.32 Overall, roughly one third of the
patients receiving unrelated PBSC or BM developed moderate-to-severe
acute GVHD, which is less than that reported by others using unrelated
marrow.33,34 One reason for this may be that, in addition
to methotrexate and cyclosporine, some patients received ATG, which may
reduce the incidence of acute GVHD.35 However, an increased
incidence of GVHD was seen in the OKT3 group. The low incidence of GVHD
in the group receiving CD34-enriched cells is expected because of the
effective CD3 depletion in this group (Table 3). If T-cell depletion of
the graft is performed, the T-cell dose seems important for the
development of GVHD.36 In HLA-identical siblings, a
threshold dose for acute GVHD is estimated to be approximately 5 × 105 CD3+ cells/kg. All of the patients
receiving CD34-enriched PBSC received a lower dose. However, the
CD3+ dose was not important for acute GVHD in this limited
material. Moreover, the patients receiving CD34-selected grafts also
received ATG.
So far, no patient in the CD34 group has developed chronic GVHD. This
may be due to the close correlation between acute GVHD and chronic
GVHD.37,38 The probability of chronic GVHD was the same in
the PBSC and the BM groups. It was thought that PBSC, because of its
high cell content, would increase the risk of chronic GVHD. For
instance, treatment with donor buffy coat cells in association with
transplantation increases the risk of chronic GVHD.37 Two studies found an increased risk of chronic GVHD in HLA-identical siblings receiving PBSC compared with BM.39,40 This was not seen in our study of unrelated PBSC versus BM. The reason for this may
be the high risk of chronic GVHD even with unrelated BM, which is
greater than 80%, compared with approximately 40% in HLA-identical
siblings.33,34,37,38
With regards to survival, relapse, and relapse-free survival, there was
no difference between outcome in patients receiving PBSC compared with
the BM controls (Figs 5, 6, and 7). This is in agreement with the
experience of PBSC versus BM in HLA-identical siblings.6,10
It was hoped that the higher T-cell content in PBSC would have a
stronger antileukemic effect than that seen with BM. However, the
antileukemic effect may be induced by activated T cells during acute
and chronic GVHD rather than inactive T cells of a T-replete
graft.41-43 Our follow-up of the patients was rather short,
and the survival and relapse data must therefore be viewed with
caution. However, the outcome is in line with the experience in
HLA-identical siblings.6,10 Because the number of patients receiving CD34-selected cells was small, they were not matched with the
other two groups, and the observation time was short, care should be
taken regarding the interpretation of the outcome. There was a trend
for more high-risk patients in the CD34 group, compared with the other
two groups (Table 1). The risk-factors for survival and LFS in this
study (disease-stage, age, acute leukemia versus CML, acute GVHD, and
absence of chronic GVHD) are in accordance with previous
publications.33,34,41,43
Despite the limitations of the study, we conclude that transplantation
of PBSC from unrelated donors is a safe procedure and results in a
faster engraftment than with BM. It was also reported previously that
PBSC resulted in a better immune reconstitution than with
BM.44 Apart from these advantages for the recipient, there
may be several advantages for the donor than with donation of BM. There
is no need for hospitalization, general anesthesia, and blood
transfusions. Instead, the donors are subjected to the risks of
treatment with G-CSF, which include skeletal pain and thrombocytopenia
after leukapheresis. A rare complication in one donor was splenic
rupture.45 Thrombosis may be a risk, and 2 patients
developed vascular side effects after donation of PBSC: 1 cerebrovascular accident and 1 myocardial infarction.46 In the long term, there will probably be little risk for the donor. Although unlikely, the question has been raised as to whether G-CSF
mobilization of PBSC may increase the risk of leukemia. It has also
been discussed whether repeated treatment of G-CSF can cause marrow
exhaustion and pancytopenia. Because of these concerns, it is important
to observe PBSC donors for several years after the donations. In the
Nordic countries, PBSC donors will be observed and registered at 3-year
intervals and compared with BM donors and registered to the national
survival and cancer registries. However, a large number of PBSC donors
and a long follow-up will be required before these issues can be settled.
It is expected that the use of PBSC from unrelated donors will increase
in the same way as PBSC from HLA-identical siblings because of its
benefits for the recipient and the donor.
| |
ACKNOWLEDGMENT |
The authors thank the staff at the various units for expert patient
care. We thank Inger Hammarberg for excellent typing of the manuscript.
| |
FOOTNOTES |
Submitted December 15, 1998; accepted March 23, 1999.
Supported by grants from the Swedish Cancer Foundation
(0070-B95-09XCC), the Children's Cancer Foundation (1995/035), the Swedish Medical Research Council (B96-16X-05971-16C), the FRF Foundation, the Tobias Foundation, and the Ellen Bachrach Foundation.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address reprint requests to O. Ringdén, MD, PhD, Department of
Clinical Immunology, Huddinge Hospital, F79, SE-141 86 Huddinge,
Sweden; e-mail: olle.ringden{at}immunlab.hs.sll.se.
| |
REFERENCES |
1.
Dreger P, Suttorp M, Haferlach T, Löffler H, Schmitz N, Schroyes W:
Allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for treatment of engraftment failure after bone marrow transplantation.
Blood
81:1404, 1993[Free Full Text]
2.
Russel NH, Hunter AE:
Peripheral blood stem cells for allogeneic transplantation.
Bone Marrow Transplant
13:353, 1994[Medline]
[Order article via Infotrieve]
3.
Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J, Storb R, Buckner CD:
Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor.
Blood
85:1655, 1995[Abstract/Free Full Text]
4.
Körbling M, Przepiorka D, Huh YO, Engel H, van Besien K, Giralt S, Andersson B, Kleine HD, Seong D, Deisseroth AB, Andreeff M, Champlin R:
Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: Potential advantage of blood over marrow allografts.
Blood
85:1659, 1995[Abstract/Free Full Text]
5.
Schmitz N, Dreger P, Suttorp M, Rohwedder EB, Haferlach T, Löffler H, Hunter A, Russel NH:
Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by Filgrastim (G-CSF).
Blood
85:1666, 1995[Abstract/Free Full Text]
6.
Bensinger WI, Clift R, Martin P, Appelbaum FR, Demirer T, Gooley T, Lilleby K, Rowley S, Sanders J, Storb R, Buckner CD:
Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: A retrospective comparison with marrow transplantation.
Blood
88:2794, 1996[Abstract/Free Full Text]
7.
Schmitz N, Bacigalupo A, Labopin M, Majolino I, Laporte J-P, Brinch L, Cook G, Deliliers GL, Lange A, Rozman C, Garcia-Conde J, Finke J, Domingo-Albos A, Gratwohl A, on behalf of the European Group for Blood and Marrow Transplantation (EBMT):
Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors.
Br J Haematol
95:715, 1996[Medline]
[Order article via Infotrieve]
8.
Briones J, Urbano-Ispizua A, Lawler M, Rozman C, Gardiner N, Marín P, Salgado C, Féliz P, McCann S, Montserrat E:
High frequency of donor chimerism after allogeneic transplantation of CD34+-selected peripheral blood cells.
Exp Hematol
26:415, 1998[Medline]
[Order article via Infotrieve]
9.
Bacigalupo A, Zikos P, Van Lint M-T, Valbonesi M, Lamparelli T, Gualandi F, Occhini D, Mordini N, Bregante S, Berisso G, Vitale V, Sessarego M, Marmont AM:
Allogeneic bone marrow or peripheral blood cell transplants in adults with hematologic malignancies: A single-center experience.
Exp Hematol
26:409, 1998[Medline]
[Order article via Infotrieve]
10.
Schmitz N, Bacigalupo A, Hasenclever D, Nagler A, Gluckman E, Clark P, Bourquelot P, Greinix H, Frickhofen N, Ringdén O, Zander A, Apperley JF, Gorin C, Borkett K, Schwab G, Goebel M, Russel NH, Gratwohl A:
Allogeneic bone marrow transplantation vs. Filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: First results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation.
Bone Marrow Transplant
21:995, 1998[Medline]
[Order article via Infotrieve]
11.
Ringdén O, Lönnqvist B, Hägglund H, Ljungman P, Shanwell A, Lawlor E, Schmitz N:
Transplantation with peripheral blood stem cells from unrelated donors without serious graft-versus-host disease (letter).
Bone Marrow Transplant
16:856, 1995[Medline]
[Order article via Infotrieve]
12.
Stockschläder M, Löliger C, Krüger W, Zeller W, Heyll A, Schönrock-Nabulsi P, Zander A:
Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor.
Bone Marrow Transplant
16:719, 1995[Medline]
[Order article via Infotrieve]
13.
Ringdén O, Hägglund H, Runde V, Basu O, Kroschinsky F, Stockschläder M, Potter MN:
Faster engraftment of peripheral blood progenitor cells compared to bone marrow from unrelated donors.
Bone Marrow Transplant
21:S81, 1998 (suppl 3)
14.
Hägglund H, Ringdén O, Remberger M, Lönnqvist B, Sparrelid E, Tammik L, Kumlien G:
Faster neutrophil and platelet engraftment, but no differences in acute GVHD or survival, using peripheral blood stem cells from related and unrelated donors, compared to bone marrow.
Bone Marrow Transplant
22:131, 1998[Medline]
[Order article via Infotrieve]
15.
Bensinger WI, Price TH, Dale DC, Appelbaum FR, Clift R, Lilleby K, Williams B, Storb R, Thomas ED, Buckner CD:
The effects of daily recombinant human granulocyte colony stimulating factor administration on normal granulocyte donors undergoing leukapheresis.
Blood
81:1883, 1993[Abstract/Free Full Text]
16.
Dreger P, Haferlach T, Eckstein V, Jacobs S, Suttorp M, Löffler H, Müller-Ruchholtz W, Schmitz N:
G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation: Safety, kinetics of mobilization, and composition of the graft.
Br J Haematol
87:609, 1994[Medline]
[Order article via Infotrieve]
17.
Olerup O, Zetterquist H:
HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: An alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation.
Tissue Antigens
39:225, 1992[Medline]
[Order article via Infotrieve]
18.
Bornhäuser M, Hölig K, Rautenberg U, Ordemann R, Kroschinsky F, Naumann R, Schuler U, Ehninger G:
Allogeneic transplantation of G-CSF mobilised CD34 positive selected peripheral blood stem cells from unrelated and HLA-mismatched donors.
Blood
90:106a, 1997 (abstr, suppl 1)
19.
Ringdén O, Remberger M, Persson U, Ljungman P, Aldener A, Andström E, Aschan J, Bolme P, Dahllöf G, Dalianis T, Gahrton G, Hägglund H, Lönnqvist B, Olerup O, Shanwell A, Sparrelid E, Winiarski J, Öberg M, Möller E:
Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings.
Bone Marrow Transplant
15:619, 1995[Medline]
[Order article via Infotrieve]
20.
Beelen DW, Ottinger HD, Elmaagacli A, Scheulen B, Basu O, Kremens B, Havers W, Grosse-Wilde H, Schaefer U:
Transplantation of Filgrastim-mobilized peripheral blood stem cells from HLA-identical sibling or alternatively family donors in patients with hematologic malignancies: A prospective comparison of clinical outcome, immune reconstitution and hematopoietic chimerism.
Blood
90:4725, 1997[Abstract/Free Full Text]
21.
Storb R, Deeg HJ, Farewell K, Doney K, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Hansen J, Hill R, Longton G, Lum L, Martin P, McGuffin R, Sanders J, Singer J, Stewart P, Sullivan K, Witherspoon R, Thomas ED:
Marrow transplantation for severe aplastic anemia: Methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease.
Blood
68:119, 1986[Abstract/Free Full Text]
22.
Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD:
Bone-marrow transplantation. Parts I and II.
N Engl J Med
292:832, 1975[Medline]
[Order article via Infotrieve], 895
23.
Shulman HM, Sullivan KM, Weiden Pl, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi M-S, Storb R, Thomas ED:
Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients.
Am J Med
69:204, 1980[Medline]
[Order article via Infotrieve]
24.
Einsele H, Steidle M, Valbracht A, Saal J, Ehringer G, Müller C:
Early occurrence of HCMV infection after BMT as demonstrated by the PCR technique.
Blood
77:1104, 1991[Abstract/Free Full Text]
25.
Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG:
Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples.
Br J Cancer
35:1, 1977[Medline]
[Order article via Infotrieve]
26.
Cox DR:
Regression models and life-tables.
J R Stat Soc B
34:187, 1972
27.
Ringdén O, Bäckman L, Lönnqvist B, Heimdahl A, Lindholm A, Bolme P, Gahrton G:
A randomized trial comparing the use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematologic malignancies.
Bone Marrow Transplant
1:41, 1986[Medline]
[Order article via Infotrieve]
28. Hägglund H, Ringdén O, Öhman S, Remberger
M, Carlens S, Mattsson J: A prospective randomized trial of Filgrastim
(r-metHuG-CSF) given at different times after unrelated bone marrow
transplantation. Bone Marrow Transplant (in press)
29.
Mavroudis D, Read E, Cottler-Fox M, Couriel D, Molldrem J, Carter C, Yu M, Dunbar C, Barrett J:
CD34+ cell dose predicts survival, posttransplant morbidity and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies.
Blood
88:3223, 1996[Abstract/Free Full Text]
30.
Ringdén O, Deeg HJ, Beschorner W, Slavin S:
Effector cells of graft-versus-host disease, host resistance and the graft-versus-leukemia effect: Summary of a workshop on bone marrow transplantation.
Transplant Proc
19:2758, 1987[Medline]
[Order article via Infotrieve]
31.
Marmont A, Horowitz MM, Gale RP, Ash RC, van Bekkum DW, Champlin RE, Dicks KA, Goldman JM, Good RA, Herzig RM, Hung R, Masaoke T, O'Reilly RD, Prentice HG, Rimm AA, Ringdén O, Speck B, Weiner RS, Bortin MM:
T-cell depletion of HLA-identical transplants in leukemia.
Blood
78:2120, 1991[Abstract/Free Full Text]
32.
Ringdén O, Nilsson B:
Death by graft-versus-host disease associated with HLA mismatch, high recipient age, low marrow cell dose and splenectomy.
Transplantation
40:39, 1985[Medline]
[Order article via Infotrieve]
33.
Beatty PG, Hansen JA, Longton GM, Thomas ED, Sanders JE, Martin PJ, Bearman SI, Anasetti C, Petersdorf EW, Mickelson EM, Pepe MS, Appelbaum FR, Buckner CD, Clift RA, Petersen FB, Stewart PS, Storb RF, Sullivan KM, Tesler MC, Witherspoon RP:
Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies.
Transplantation
51:443, 1991[Medline]
[Order article via Infotrieve]
34.
Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, Gajewski J, Hansen JA, Henslee-Downey J, McGullough J, McGlave P, Perkins HA, Philips GL, Sanders J, Stroncek D, Thomas ED, Blume KG:
Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program.
N Engl J Med
328:592, 1993[Free Full Text]
35.
Ringdén O, Remberger M, Carlens S, Hägglund H, Mattsson J, Aschan J, Lönnqvist B, Klaesson S, Winiarski J, Dalianis T, Olerup O, Sparrelid E, Svahn BM, Ljungman P:
Low incidence of acute graft-versus-host disease, using unrelated HLA-A, -B and -DR compatible donors and conditioning including anti-T-cell antibodies.
Transplantation
66:620, 1998[Medline]
[Order article via Infotrieve]
36.
Ringdén O, Pihlstedt P, Markling L, Aschan J, Båryd I, Ljungman P, Lönnqvist B, Tollemar J, Janossy G, Sundberg B:
Prevention of graft-versus-host disease with T-cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients.
Bone Marrow Transplant
7:221, 1991[Medline]
[Order article via Infotrieve]
37.
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen J, Hill R, Lum L, Martin P, McGuffin R, Sanders J, Stewart P, Sullivan K, Witherspoon R, Yee G, Thomas ED:
Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia.
N Engl J Med
314:729, 1986[Abstract]
38.
Ringdén O, Paulin T, Lönnqvist B, Nilsson B:
An analysis of factors predisposing for chronic graft-versus-host disease.
Exp Hematol
13:1062, 1985[Medline]
[Order article via Infotrieve]
39.
Storek J, Gooley T, Siadak M, Bensinger WI, Maloney DG, Chauncey TR, Flowers M, Sullivan KM, Witherspoon RP, Rowley SD, Hansen JA, Storb R, Appelbaum FR:
Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease.
Blood
90:4705, 1997[Abstract/Free Full Text]
40.
Scott MA, Gandhi MK, Jestice HK, Mahendra P, Bass G, Marcus RE:
A trend towards an increased incidence of chronic graft-versushost disease following allogeneic peripheral blood progenitor cell transplantation: A case-controlled study.
Bone Marrow Transplant
22:273, 1998[Medline]
[Order article via Infotrieve]
41.
Weiden PL, Fluornoy N, Thomas ED, Prentice R, Feifer A, Buckner CD, Storb R:
Anti-leukemic effect of graft-versus-host disease in human recipients of allogeneic marrow grafts.
N Engl J Med
300:1068, 1979[Abstract]
42.
Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb H-J, Rimm AA, Ringdén O, Rozman C, Speck B, Truitt RL, Zwaan FE, Bortin MM:
Graft-versus-leukemia reactions following bone marrow transplantation in humans.
Blood
75:555, 1989[Abstract/Free Full Text]
43.
Ringdén O, Labopin M, Gluckman E, Reiffers J, Vernant JP, Jouet JP, Harousseau JL, Fiere D, Bacigalupo A, Frassoni F, Gorin NC, and for the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation:
Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis.
Bone Marrow Transplant
18:921, 1996[Medline]
[Order article via Infotrieve]
44.
Ottinger HD, Beelen DW, Scheulen B, Schaefer UW, Grosse-Wilde H:
Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow.
Blood
88:2775, 1996[Abstract/Free Full Text]
45.
Becker PS, Wagle M, Matous S, Swanson RS, Pihan G, Lowry PA, Stewart FM, Heard SO:
Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): Occurrence in an allogeneic donor of peripheral blood stem cells.
Biol Blood Marrow Transplant
3:45, 1997[Medline]
[Order article via Infotrieve]
46.
Anderlini P, Przepiorka D, Körbling M, Champlin R:
Blood stem cell procurement: Donor safety issues.
Bone Marrow Transplant
21:S35, 1998 (suppl 3)
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ABSTRACT
INTRODUCTION
