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Bone Marrow Transplantation, (1998) 22, 1145–1151

 1998 Stockton Press All rights reserved 0268–3369/98 $12.00


http://www.stockton-press.co.uk/bmt

A randomised, prospective comparison of allogeneic bone marrow and


peripheral blood progenitor cell transplantation in the treatment of
haematological malignancies

AC Vigorito, WM Azevedo, JFC Marques, AM Azevedo, KAB Eid, FJP Aranha, I Lorand-Metze,
GB Oliveira, MEP Correa, ARC Reis, ECM Miranda and CA de Souza
Bone Marrow Transplantation Unit, State University of Campinas, SP, Brazil

Summary: ised by growth factors have shown advantages over bone


marrow cells in terms of ease of collection and favourable
We present the results of a prospective, randomised kinetics of haematopoietic reconstitution leading to acceler-
study comparing PBPC and BM focusing on ated platelet and neutrophil recovery.5–9 The use of rhG-
engraftment, acute and chronic GVHD and survival. CSF for mobilisation of progenitor cells into the circulation
Forty patients with haematological malignancies is safe and has already been extensively utilised in autolog-
received HLA-identical sibling BM (group A) or PBPC ous transplantation, with a side-effect profile that makes
(group B). Evaluable patients were 19 (A) and 18 (B). it a reasonable option for normal donors.5,10,11 The most
Median age was 35 (17–56) in A and 29.5 (9–51) in B. important problems related to the PBPC transplant seem to
Conditioning was mainly Bu-Cy2; GVHD prophylaxis be those associated with incidence and severity of chronic
was CSA-MTX. PBPC were harvested after 5 days of GVHD (c-GVHD). Data from Seattle and other groups sug-
G-CSF 10 ␮g/kg/day. Median days for an ANC gest that the incidence of c-GVHD may be higher after
⬎0.5 ⴛ 109/l was 18 (13–30) in A and 16 (11–25) in B PBPC than after marrow grafting.12–15 The hazard of
(P = 0.10). Platelets ⬎20 ⴛ 109/l occurred at ⴙ17 (10– developing clinical extensive c-GVHD by 2 years was 2.37
40) in A and ⴙ12 (9–36) in B (P = 0.01). The probability times higher among PBPC than marrow recipients.12 How-
of ⭓2 grade a-GVHD was 19% (A) and 27% (B) ever, few formal comparisons have been made between the
(P = 0.53). The probability of all grade c-GVHD was outcomes of patients receiving HLA-identical allogeneic
70% with BM. In spite of the small number of patients PBPC transplants and those receiving BM transplants.9
in group B (PBPC), our data suggest the great majority Randomised studies have been undertaken by many centres,
of them will have c-GVHD (P = 0.08); extensive disease but no published data have been available to date. There-
was present in 50 and 100%, respectively (P = 0.05). The fore, following a previous pilot study5 we began a con-
estimates of overall survival for A and B at 1000 days trolled, randomised study aiming at comparing primarily
are 51 and 47%, respectively (P = 0.67); DFS at 1000 survival, and secondly, engraftment kinetics, incidence and
days are 52 and 58%, respectively (P = 0.50). PBPC severity of acute and chronic GVHD in allogeneic bone
resulted in faster platelet engraftment. The incidence of marrow transplantation for haematological malignancies.
acute and chronic GVHD was similar in both groups,
but the severity of c-GVHD was higher with PBPC. No
differences in survival and DFS have been observed to
date.
Keywords: Peripheral blood progenitor cell; allogeneic Patients and methods
transplantation; chronic GVHD

Eligibility criteria
Bone marrow (BM) has been the standard source of cells This study was a prospective randomised, phase III trial
to rescue lympho-haematopoiesis after myeloablative ther- performed in a single institution. It began in February 1995
apy but recently allogeneic peripheral blood progenitor and closed in October 1997. All patients had at least 100
cells (PBPC) have been replacing bone marrow for autolog- days of follow-up after transplantation. Eligibility criteria
ous transplants.1–4 Moreover, pilot and retrospective studies for entry into the study were age between 10 and 60 years,
suggest that HLA-identical PBPC can also restore haemo- haematological malignancy as primary disease and HLA-
poiesis without an increase in the incidence or severity of identical sibling donors. A detailed explanation about the
acute graft-versus-host-disease (a-GVHD).5–9 PBPC mobil- procedure and its potential complications were given to
patients and donors. Informed consent was obtained using
Correspondence: CA de Souza, Hemocentro/Unicamp, PO Box 6198, protocols and forms according to our institution regulations.
Barão Geraldo, 13081–970, Campinas, SP, Brasil Patients, donors and treatment characteristics are shown
Received 22 May 1998; accepted 30 July 1998 in Table 1.
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AC Vigorito et al

1146
Table 1 Patient, donor and treatment characteristics Evaluations and definitions

PBPC BM PBPC and BM were analysed for CD34+ cells and T cell
subsets by flow cytometry as previously described.18 Mono-
Patients (No.) 18 19 clonal antibodies were obtained from Becton Dickinson
Age in years, median (range) Immunocytometry Systems (San Jose, CA, USA).
Patients 29.5 (9–51) 35 (17–56) CD34-positive cells were quantified using a modification
Donors 30 (14–60) 32 (12–60) of the method described by Sutherland et al.18 In this modi-
Patient gender M = 12 M = 15
F=6 F=4 fication, the antibody CD14/FITC was used instead of
Donor gender M→M=4 M→M=7 CD45 to exclude myeloid/monocytic cells contaminating
M→F=1 M→F=2 the CD34/PE-positive population defined as CD14 negative
F→M=8 F→M=8 and presenting a low side scatter.
F→F=5 F→F=2
Early disease T cell subsets were analysed by the whole blood
(CML, 1st CP; AML, 1st CR; AML, 13 13 lyse/wash method using the monoclonal antibodies CD3-
1st rel; ALL, 1st CR; MDS-RA) FITC/CD4-PE, CD3-FITC/CD8-PE and CD4-FITC/CD8-
Advanced disease PE. All data were collected and analysed in the FACscali-
(CML, AP/BC; AML ⬎ 1st rel; 5 6 bur flow cytometry equipment (Becton Dickinson), using
refractory AML, MM, NHL;
ALL ⬎ 2nd; MDS-RAEB) the software Cell Quest.
Alive 10 10 Neutrophil engraftment was defined as the first of 2 con-
Dead 8 9 secutive days with an absolute neutrophil count (ANC)
Follow-up (days) 335 631 ⬎0.5 × 109/l following a post-transplant nadir. Platelet
(120–1079) (281–1044)
Myeloablative regimens engraftment was defined as the first of 7 consecutive days
Bu (16)/Cy (120) 17 16 with a platelet count ⬎20 × 109/l without platelet trans-
Bu (16)/Cy (120)/VP-16 (40) — 3 fusion. Engraftment was also documented by marrow aspir-
CY (120)/TBI (13.2 Gy) 1 — ation, biopsy and cytogenetics.
GVHD prophylaxis Assessment and grading of a-GVHD and c-GVHD were
CSP/MTX 18 16
CSP/Pred — 3 made using the Glucksberg19 and Shulman criteria,20
respectively. Supportive care was provided in private rooms
M = male; F = female; CML = chronic myeloid leukaemia; CP = chronic equipped with HEPA filters. Irradiated red blood cell and
phase; AML = acute myeloid leukaemia; rel = relapse; ALL = acute lym- platelet transfusions, as well as broad-spectrum antibiotics
phoblastic leukaemia; CR = complete remission; MDS =myelodysplastic together with anti-fungal agents, were given whenever indi-
syndrome; RA = refractory anaemia; AP/BC = accelerated phase/blastic cated. Ceftazidime was started as soon as the neutrophil
crisis; MM = multiple myeloma; NHL = non-Hodgkin’s disease;
RAEB = refractory anaemia with excess of blast; Bu (16) = busulfan (16 count dropped below 0.5 × 109/l and changes were made as
mg/kg); Cy (120) = cyclophosphamide (120 mg/kg); VP-16 = etoposide indicated by cultures and clinical course, keeping the
(40 mg/kg); TBI = total body irradiation; CSP = cyclosporine; patient on antibiotics until the granulocyte count reached
MTX = methotrexate; Pred = prednisone. 1.0 × 109/l. All patients received ganciclovir (5 mg/kg/day
3 times a week) after marrow recovery as cytomegalovirus
(CMV) infection prophylaxis until day 75 post-transplant.
Nutritional support, including total intravenous nutrition,
was provided to assure an adequate nutritional balance.
Donors
All PBPC donors received rhG-CSF (Granulokine; Roche, Statistical methods
SP, Brazil) by subcutaneous injection (10 ␮g/kg daily for
5 consecutive days). Apheresis was performed on day 5 of Analysis was based on status of the patients on 1 February
G-CSF administration. Day 5 rhG-CSF donor adminis- 1998. Our main objective was to compare overall survival
tration was timed to coincide with day 0 of the allograft and then compare objective response rates, disease-free sur-
recipient. Leukaphereses were performed by a Dideco Viv- vival and toxicity. Overall survival (OS) in both groups was
acell (Mod. BT-798 CE/A; Mirandola, Italy) continuous measured from the date of randomisation to the date of
flow blood cell separator using a standard leukocyte apher- death or last follow-up evaluation. Disease-free survival
esis program. The collection usually lasted 3–5 h and a only applies to patients who achieved a complete remission.
vein-to-vein technique was used to avoid use of an indwell- Duration was calculated from the time of CR assessment to
ing catheter. After collection, the apheresis product was the date of relapse or last follow-up evaluation confirming
infused into recipients immediately. A goal of this study freedom from disease. All data were analysed with descrip-
was to collect and infuse a minimum of 2 × 108 of total tive statistical methods. Probability of events (neutrophil
mononuclear cells (TMNC).16 and platelet recovery, a-GVHD, c-GVHD) and survival
Bone marrow was obtained from donors by standard curves were analysed using Kaplan–Meier21 product limit
methods.17 Day 0 for the recipient was defined as the day estimates, and groups were compared using the log-rank
of BM or PBPC infusion. test or Breslow’s test with SPSS software version 7.5 for
A summary of pre-treatment preparative regimens and Windows 95. Proportions of patients within each group of
GVHD prophylaxis is shown in Table 1. No growth factors characteristics and outcome for patients receiving PBPC or
were used after transplantation. BM were compared by the Fisher’s test or ␹2 test, when
ABMT and PBPCT in haematological malignancies
AC Vigorito et al

1147
appropriate. Comparisons of continuous variables were also Table 2 Graft characteristics
performed with the Mann–Whitney test, considering all P
values ⬍0.05 significant. PBPC (M) BM (M) P

Nucleated cells/kg (108) 5.5 2.6 ⬍0.0001


Results Mononuclear cells/kg (108) 3.2 1.1 ⬍0.0001
CD34/kg (106) 4.7 5.3 0.47
CD3/kg (106) 317.0 75.7 ⬍0.0001
During the study, 40 patients were randomised; 18 received CD3/CD4+/kg (106) 154.5 39.2 ⬍0.0001
PBPC and 19 received BM. Three patients were excluded CD3/CD8+/kg (106) 97.3 28.0 ⬍0.0001
from the analysis: two in the PBPC group, where one ref-
used and the other had no HLA-identical sibling, and one M = median.
in the BM group because they did not have a haematolog-
ical malignancy.
Table 3 Engraftment and transfusions

Donors PBPC (M) BM (M) P

All donors received the proposed dose of rhG-CSF. Leu- Day ANC ⬎0.5 × 109/l
kapheresis procedures and rhG-CSF were generally well Median (range) +16 (11–25) +18 (13–30) 0.15a
tolerated. The median total blood processed was 12.0 l Day platelets ⬍20 × 109/l
(9.4–28.5). The median white blood cell count on day 5 of Median (range) +12 (9–36) +17 (10–40) 0.01a
rhG-CSF was 31.7 × 109/l (12.3–62.5). No side-effects with No. of platelets units transfused
Median (range) 12.5 (4–44) 17.5 (1–341) 0.32
rhG-CSF were observed in seven of 18 donors (39%). Mild No. of RBC units transfused
bone pain occurred in eight out of 18 donors (44%) whereas Median (range) 4 (2–12) 5 (1–75) 0.20
two of 18 (11%) experienced headache. All donors showed Days to discharge
a decrease in platelet counts after apheresis. The median Median (range) +21 (18–42) +26 (18–48) 0.08
pre-apheresis platelet count was 239.5 × 109/l (149.0– a
369.0) and post-apheresis it was 119.0 × 109/l (58.0–217.0) Breslow’s test.
ANC = absolute neutrophil count; RBC = red blood cells.
(P ⬍ 0.0001). Seven of 18 donors (39%) had platelet
reductions below 100 × 109/l. However, no bleeding epi-
sodes occurred. There were no relevant changes in hema- reach an ANC of 0.5 × 109/l, the median day to achieve
tocrit. No significant problems were seen during apheresis such a count was 16 (11–25) for recipients of PBPC and
despite the large volume of blood that was processed. 18 (13–30) for recipients of BM. The median period to
achieve a count of ⬎0.5 × 109/l neutrophils was not sig-
Comparability of PBPC and BM groups nificantly shorter for patients receiving PBPC (P = 0.15)
(Figure 1).
As shown in Table 1, PBPC and BM groups were well One patient receiving PBPC developed progression of
matched for diagnosis, age, phase of disease and treatment. his primary disease before reaching platelet transfusion
Recipients of allogeneic PBPC received a median of independence. Two patients in each group died before
5.5 × 108/kg (2.2–21.0) total nucleated cells (TNC); reaching platelet transfusion independence. One patient in
3.2 × 108/kg (2.0–5.4) total mononuclear cells (TMNC); the BM group was not evaluable due to primary
4.7 × 106/kg (1.26–71.6) CD34+ cells; 317.0 × 106/kg engraftment failure. The median day to achieve platelet
(160.6–644.7) CD3+ cells; 154.5 × 106/kg (23.6–12.2) independence was day 12 (9–36) for the PBPC group and
CD3+/CD4+ cells; and 97.3 × 106/kg (45.7–217.5)
CD3+/CD8+ cells. All patients, except two, received a
1.0
single apheresis product.
Recipients of BM received a median of 2.6 × 108/kg
(1.5–3.4) total nucleated cells (TNC); 1.1 × 108/kg (0.6– 0.8
1.9) total mononuclear cells (TMNC); 5.3 × 106/kg (1.2–
BM
17.5) of CD34+ cells; 75.7 × 106/kg (26.4–157.3) CD3+ PBPC
Probability

cells; 39.2 × 106/kg (11.0–64.3) CD3+/CD4+ cells; and 0.6


28.0 × 106/kg (10.0–97.4) CD3+/CD8+ cells.
All values, except number of CD34+ cells (P = 0.47), 0.4
were significantly higher in the PBPC group (Table 2).

0.2
Engraftment and transfusion requirements
Parameters of engraftment and transfusion requirements are
0
shown in Table 3. One patient transplanted with PBPC died 0 5 10 15 20 25 30
and one developed disease progression before reaching neu-
Days
trophils ⬎0.5 × 109/l. One patient transplanted with BM
had primary engraftment failure. Among those who did Figure 1 Probability of 0.5 × 109/l granulocytes.
ABMT and PBPCT in haematological malignancies
AC Vigorito et al

1148
1.0 1.0

PBPC
0.8 0.8
BM
Probability

0.6 0.6

Probability
0.4 0.4
PBPC
0.2 0.2 BM

0 0
0 10 20 30 40 0 20 40 60 80 100
Days Days

Figure 2 Probability of 20 × 109/l platelets. Figure 3 Probability of a-GVHD grades 2–4.

Table 5 Organs involved with c-GVHD


day 17 (10–40) for the BM group. This was significantly
shorter for patients receiving PBPC compared to BM Organ PBPC (%) BM (%) P
(P = 0.01) (Figure 2).
The median number of platelet units transfused was 12.5 Skin 2 (20) 1 (12.5) 0.5a
(4–44) in the group receiving PBPC compared to 17.5 (1– Liver 10 (100) 8 (100) —
Eyes 5 (50) 1 (12.5) 0.1a
341) for the BM group (P = 0.32). The median number of Mouth 9 (90) 3 (37.5) 0.03a
units of red blood cells transfused was 4 (2–12) in the Lung 0 1 (12.5) 0.4a
PBPC group compared to 5 (1–75) in the BM group (bronchiolitis obliterans)
(P = 0.20).
a
There were no engraftment failures in the PBPC group, Fisher’s test.
but one primary failure was seen in the BM group. This
patient did not respond to G-CSF and was therefore treated
patients transplanted with PBPC and 19% for patients trans-
with mobilised PBPC obtained from the original BM donor. planted with BM (P = 0.53) (Figure 3).
Engraftment of neutrophils occurred on day 24, and plate-
Clinical chronic GVHD of all grades developed in 10
lets on day 28 after infusion. The patient developed exten-
out of 14 (71.4%) evaluable PBPC recipients and in eight
sive c-GVHD on day 348 but is alive and well receiving out of 15 (53.3%) BM recipients (P = 0.53) (Table 4).
cyclosporin and prednisone.
Table 5 shows the areas involved by c-GVHD. No differ-
ence was observed, except for more mouth involvement in
Acute and chronic GVHD the PBPC group (P = 0.03) (Table 5). Although the number
of evaluable cases receiving PBPC is small, our data sug-
As shown in Table 4, the incidence of grades 2 to 4 acute
gest that the great majority will have c-GVHD of all grades,
GVHD was four out of 15 (26.6%) evaluable PBPC com- whereas for patients transplanted with BM the probability is
pared to three out of 16 (18.7%) patients who were trans-
70% (P = 0.08) (Figure 4). All patients in the PBPC group
planted with BM (P = 0.40). Grades 3 to 4 acute GVHD
occurred in two out of four and in two out of three patients
receiving PBPC or BM, respectively. The probabilities of 1.0
developing grades 2 to 4 acute GVHD were 27% for
0.8

Table 4 Incidence of a-GVHD and c-GVHD PBPC


Probability

0.6
PBPC BM P BM
0.4
Acute GVHD evaluable 15 16
Grade 2–4 4/15 (26/6%) 3/16 (18.7%) 0.40a
Grade 3–4 2/4 2/3
0.2
Chronic GVHD evaluable 14 15
Total affected 10/14 (71.4%) 8/15 (53.3%) 0.53b
Extensive 10/10 (100%) 4/8 (50%) 0.02a
Limited 0 4/8 (50%) 0.02a 0
0 1 2 3
Years
a
Fisher’s test.
␹ test.
b 2
Figure 4 Probability of total affected c-GVHD.
ABMT and PBPCT in haematological malignancies
AC Vigorito et al

1149
developed extensive chronic GVHD while four out of eight 1.0
(50%) developed extensive chronic GVHD in the BM
group (P = 0.02). 0.8

Causes of death

Probability
0.6 BM = 51%
As shown in Table 6, five out of eight (62.5%) of the cases
receiving PBPC died of transplant-related complications as PBPC = 47%
0.4
compared to seven out of nine (77.8%) who received BM.
There were two deaths from bacterial infection in the PBPC
group and one in the BM group. One death occurred from 0.2
gastric-intestinal CMV and one from hepatic veno-occlus-
ive disease (VOD). There was one case of haemorrhagic
0
cystitis in the BM group. No deaths due to CMV, VOD or
0 1 2 3
haemorrhage were seen in the PBPC group. One patient in Years
each group died of a-GVHD and two patients in each group
died of c-GVHD. In both groups, all relapsed or pro- Figure 5 Overall survival.
gressing patients died, three out of eight patients (37.5%)
in the group receiving PBPC and two out of nine patients 1.0
(22.2%) in the BM group.

0.8
Relapse
Among patients transplanted with PBPC, two out of 18 PBPC = 58%
Probability

0.6
(11%) patients have relapsed and one out of 18 (5.5%) had
early disease progression. In patients transplanted with BM, BM = 52%
two out of 19 (10.5%) have relapsed. 0.4

Survival 0.2

Ten out of 18 (55.5%) patients who received PBPC have


survived after a median of 335 days (120–1079). In the BM 0
group 10 out of 19 (52.6%) have survived after a median 0 1 2 3
of 631 days (281–1044). The estimates of overall survival Years
for the PBPC and BM groups at 1000 days are 47 and 51%, Figure 6 Disease-free survival.
respectively (P = 0.67); DFS for the PBPC and BM groups
at 1000 days are 58 and 52%, respectively (P = 0.50)
(Figures 5 and 6). malignancies.5 In this study, PBPC were obtained by a sin-
gle apheresis. Therefore, this procedure was maintained in
the present trial.
Discussion The aim of the previous pilot project was to demonstrate
feasibility of the procedure, considering acute GVHD inci-
This study was designed taking as base a pilot project car- dence and severity, engraftment kinetics and morbidity.
ried out in our Unit in 1994 that used allogeneic PBPC Results of that pilot study and data in the literature compar-
transplantation in a group of patients with haematological ing standard BMT results, showed faster engraftment, and
shorter hospital stay for PBPC. Also, incidence and severity
of GVHD and morbidity were comparable between the two
Table 6 Causes of death groups. The current data obtained by this prospective and
randomised study seem to confirm our preliminary data and
PBPC (%) BM (%) those obtained by other authors.5–7,9
The first important observation was similar engraftment
Early progression 1 (12.5) 0 for both groups, except for platelet recovery, which was
Relapse 2 (25) 2 (22.2)
Transplant-related faster in the PBPC group (P = 0.01). In spite of the differ-
a-GVHD 1 (12.5) 1 (11.1) ence not being statistically significant, the number of plate-
c-GVHD 2 (25) 2 (22.2) let and red cells transfused was lower in the PBPC group.
Infection Procedure-related complications were also similar in num-
Bacterial 2 (25) 1 (11.1) bers. We observed no cases of primary or late engraftment
CMV — 1 (11.1)
VOD — 1 (11.1) failures in PBPC group. In the BM group, however, one
Hemorrhage — 1 (11.1) patient had primary failure of engraftment. He received
Total 8 (44.4) 9 (47.3) mobilised PBPC from the same BM donor, and attained
stable engraftment.
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AC Vigorito et al

1150
Collection of PBPC was well tolerated by donors. The counts are higher in PBPC than in marrow recipients during
dose of rhG-CSF was 10 ␮g/kg for 5 days followed by a the first 2 months, thereafter the monocyte counts are simi-
single leukapheresis with a median blood volume processed lar, whereas the T cells counts were higher in the PBPC
of 12 l on day 5. Using this standard procedure we achieved recipients for at least 6 months.30 This mechanism may be
a median of 4.7 × 106/kg CD34+ cells of recipient body associated with the higher incidence of c-GVHD. Chronic
weight, which was lower than BM yield (5.2 × 106/kg of GVHD has been associated with a low incidence of leu-
recipient). Data from the literature suggest the necessity for kaemia relapse.31,32 Therefore, allogeneic PBPC transplan-
at least two leukaphereses to obtain more than tation could also be associated with a lower incidence of
5.0 × 106/kg,6,7,10,22,23 which has been associated with a fas- relapse.14,33 In the current study we could not confirm this
ter engraftment.24 Data using only one leukapheresis and observation. Relapses were few and similar in number in
10 ␮g/kg/day by 5 days of rhG-CSF, have shown a similar both groups, which may reflect the small number of
median number of CD34+ cells (4.6 × 106/kg) compared to patients analysed.
our results.25 These data, however, suggest that our mobilis- Mortality was similar in both groups and the majority of
ation protocol was adequate, as engraftment in the PBPC deaths were procedure-related. Also, the higher frequency
group was faster with these PBPC numbers. In addition, of extensive chronic GVHD in the PBPC group correlated
long-term follow-up showed stable engraftment in all neither with death nor with worsening of life quality. It is
patients. However, the number of aphereses can be still unclear whether the benefits of fast engraftment or a
increased if necessary to obtain a higher number of CD34+ possible graft-versus-leukaemia reaction outweigh any
cells. Despite the similarity in CD34+ cell numbers infused adverse effects such as c-GVHD.6,12 In patients at high risk
in the BM and PBPC groups, the different kinetics can be of relapse, developing of c-GVHD could have beneficial
explained by the biological properties of PBPC. In autolog- effects.6
ous transplantation with PBPC where patients were mobil- We believe that allogeneic PBPC transplants should not
ised with cyclophosphamide and rhG-CSF, the PBPC were be used routinely, but only in prospective randomised trials,
insensitive to cell-cycle restraint imposed by contact with until issues regarding c-GVHD and relapse are clarified.
marrow-derived stromal cells, which therefore did not
reduce the proportion of progenitors participating in neutro-
phil production.26 Moreover, filgrastim increases numbers Acknowledgements
of circulating megakaryocyte progenitors in PBPC donors,
and this has also been associated with accelerated platelet We greatly appreciate the help of Francislaine Queiroz Costa for
recovery in recipients of autologous filgrastim-stimulated outstanding secretarial assistance and Eduardo Gasparotto Roveri
PBPC.7 for performing the apheresis procedures.
One of the greatest concerns with allogeneic PBPC trans-
plantation is the possibility of increasing incidence and
severity of GVHD due to the high number of T cells present References
in the graft.8 However, neither experimental nor clinical
data exist to show a correlation between the occurrence of 1 Sheridan WP, Begley CG, Juttner CA et al. Effect of periph-
acute GVHD and T cell number, in either BM8 or PBPC7 eral blood progenitor cells mobilised by filgrastim on platelet
transplants. The low incidence of acute GVHD in PBPC recovery after high-dose chemotherapy. Lancet 1992; 339:
transplant recipients may be attributed to G-CSF-induced 640–644.
preferential differentiation of T helper cells into Th2 rather 2 Gianni AM, Siena S, Bregni M et al. Granulocyte–macro-
Th1 cells, resulting in PBPC grafts with relatively few Th1, phage colony-stimulating factor to harvest circulating haema-
which have been implicated in the pathogenesis of acute topoietic stem cells for autotransplantation. Lancet 1989; 2:
GVHD,27 or the large number of monocytes in PBPC grafts 580–585.
that suppress T cells.28 In our study we did not find any 3 To LB, Roberts MM, Haylock DN et al. Comparison of
difference in the incidence and severity of acute GVHD in haematological recovery times and supportive care require-
ments of autologous phase peripheral blood stem cell trans-
the PBPC group compared to the BM transplant group. The
plants, autologous bone marrow transplants and allogeneic
incidence of chronic GVHD was similar but we observed bone marrow transplants. Bone Marrow Transplant 1992; 9:
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(P = 0.02). A high incidence and severity of chronic GVHD lating factor. Blood 1993; 81: 3158–3162.
after PBPC transplantation has already been reported by 5 Azevedo WM, Aranha FJ, Gouvea JV et al. Allogeneic trans-
others.12–15 In our study, involvement of various tissues was plantation with blood stem cells mobilised by rhG-CSF for
similar between groups, except for a higher incidence of hematological malignancies. Bone Marrow Transplant 1995;
16: 647–653.
oral mucosal lesions in the PBPC group (P = 0.03). Pre- 6 Bensinger WI, Weaver CH, Appelbaum F et al. Transplan-
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severe lesions of the labial salivary glands will have shorter recombinant human granulocyte colony-stimulating factor.
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ABMT and PBPCT in haematological malignancies
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1151
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