Bone Marrow Transplantation (2009) 43, 263–264
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LETTER TO THE EDITOR
G-CSF-induced thrombocytopenia in a healthy donor
Bone Marrow Transplantation (2009) 43, 263–264;
doi:10.1038/bmt.2008.310; published online 29 September 2008
starting haematopoietic stem cell mobilization and daily
during mobilization and collection (Figure 1). The plt count
started to drop on day 1 of rhG-CSF administration, and
three blood samples on day 4 provided plt counts of
77 109/l, 69 109/l and 63 109/l, respectively. As this
donor was the only one in the patient’s family, and the
CD34 þ cell count was sufficient, the leukapheresis
procedures were performed with a continuous flow blood
cell separator (COBE Spectra, Lakewood, CO, USA). The
plt count was 37 109/l afterwards. On day 6, the plt count
of 78 109/l before leukapheresis had fallen into 30 109/l
later. On day 7, as the plt count was 27 109/l, leukapheresis procedures were suspended and the plt count monitored. On days 8 and 9, it was unchanged. On day 10 (72 h
after suspending rhG-CSF), it started to rise slightly,
reaching 50 109/l whereupon the patient was discharged
from hospital. On day 16 (9 days after stopping rhG-CSF),
the plt count rebounded to 268 109/l. Pretreatment plt
counts were reached on day 37. Screening for autoimmune
disease, including detection of anti-plt antibodies, was
negative. Three abdominal ultrasound scans showed no
splenomegaly. As the CD34 þ cell harvest was insufficient
to constitute a graft, BM was explanted from the donor.
Checkups for 1 year after rhG-CSF administration showed
normal blood parameters.
During haematopoietic stem cell mobilization in healthy
donors, slight thrombocytopenia is common and is
attributed to the leukapheresis procedure or to splenomegaly.
Recombinant human G-CSF (rhG-CSF) is widely used in
haematopoietic stem cell mobilization in allogeneic transplant donors.1 rhG-CSF administration causes a mean
eightfold rise in the WBC count and a slight decrease in
haemoglobin.1 The plt count may fall slightly, possibly
because of splenomegaly, which may be enhanced by the
apheresis-related procedure.1
Here, we report a case of thrombocytopenia induced by
rhG-CSF administration in a healthy donor with no
evidence of splenomegaly before apheresis started. The
51-year-old brother of a man with multiple myeloma was
selected as matched donor for transplantation. Medical
history included two episodes of Quincke’s oedema, the
first at the age of 33 years after cephalosporine administration, and the second at the age of 43 years after
nimesulide. Clinical examination, chest X-ray, electrocardiogram, blood chemistry and urine analysis were normal.
Serology was negative for hepatitis A, B and C viruses,
HIV-1, herpes virus types 1 and 2 and toxoplasma. IgG
tests were positive for cytomegalovirus and the Epstein–
Barr virus. After providing informed consent, the donor
was admitted to hospital for s.c. infusion of rhG-CSF
(lenograstim 12 mg/kg body wt per day). WBC and plt
counts and haemoglobin level were monitored before
WBC
PLT
40000
300000
Apheresis
35000
250000
30000
200000
20000
150000
15000
100000
10000
50000
5000
0
0
0
1
2
3
4
5
6
7
8
9
14
22
Days
Figure 1 WBC and plt counts during G-CSF administration and apheresis procedure. plt recovery is also indicated.
30
PLT x 103/mmc
WBC x 103/mmc
G-CSF
25000
Letter to the Editor
264
The plt depletion is a recognized effect of continuous flow
leukapheresis, particularly large-volume leukapheresis.1
Indeed, in our large series of healthy donors, we observed
significant drops in plt counts after 3–4 leukapheresis
sessions. In animal models and in humans, rhG-CSF
administration was followed by a varying incidence and
grade of splenomegaly,2 with differences in assessment
methods underlying some of the divergent results. A
previous study3 reported that the spleen enlargement was
detected by palpation in 17% of subjects by ultrasound
measurement of longitudinal diameter in 60% and by
ultrasound calculations of spleen volume in 91%. In
patients with enlarged spleen, splenic pooling of plts leads
to thrombocytopenia, perhaps due to splenic hyperactivity.
This hypothesis was not confirmed in animal models or in
clinical observations as demonstrated by others4,5 who
showed that in humans, spleen size does not correlate with
abnormalities in haematological parameters. Several
authors described drops in plt counts, which did not reach
the pathological threshold during rhG-CSF treatment
before leukapheresis,6 and as far as we know, only two
cases of low plt counts were directly linked to rhG-CSF
administration—one in a patient with the Felty syndrome7
and the other with an underlying immune-mediated
thrombocytopenia.8 In this case, plt counts became
abnormally low during rhG-CSF administration, and we
are of the view that the drop was directly linked to therapy,
as the marked reduction was observed before starting
leukapheresis and there was no ultrasound evidence of
splenomegaly. In conclusion, the low plt count in our
patient appears to be directly linked to rhG-CSF administration. The patient’s history of allergic reactions to some
drugs, which may have enhanced the rhG-CSF plt-lowering
effect suggests that the caution and close monitoring of
haematological parameters are warranted when donors
have a similar history. The abnormally low plt count in this
donor did not prejudice haematopoietic stem cell collection,
and was short term and resolved spontaneously.
Acknowledgements
We thank Dr GA Boyd for her help.
Bone Marrow Transplantation
O Minelli1, F Falzetti2, M Di Ianni3, M Onorato1,
S Plebani3, C Silvani1 and A Tabilio3
1
Immunohematology and Blood Bank, Ospedale Santa
Maria della Misericordia, Azienda Ospedaliera di Perugia,
Perugia, Italy;
2
Hematology and Clinical Immunology Section, Department
of Clinical and Experimental Medicine, University of
Perugia, Perugia, Italy and
3
Chair of Hematology, Department of Internal Medicine and
Public Health, University of L’Aquila, L’Aquila, Italy
E-mail: [email protected]
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