Kvalheim_EU Haematology 09/03/2010 09:18 Page 27
The Use of Plerixafor for Peripheral Blood Stem Cell Mobilisation
healthy volunteers, single doses of subcutaneous plerixafor were well Table 3: Haematopoietic Stem Cell Remobilisation in
tolerated, with negative effects being mild and short-lived. The most
Six Patients at Three Scandinavian Institutions Using
common adverse events reported were gastrointestinal issues such
Granulocyte Colony-stimulating Factor and Plerixafor
as increased stool frequency, abdominal distension or bloating,
nausea and diarrhoea. Other events included injection-site erythema,
Day 4 Day 5 Day 6 Day 7 Day 8
Patient 1 Leukocytes x10
9
/l 25.4 23.5 23.2
facial/perioral paraesthesias, headache and dry mouth.
46,52,53
Patients
CD34 x10
6
/l 0.0 2.4 2.3
with NHL and MM reported similar drug-related adverse effects.
50,51
CD34 x10
6
/kg
Plerixafor given ↑
The Nordic Experience with Plerixafor in
Patient 2 Leukocytes x10
9
/l 21.1 24.1 25.4 31.2 24.0
Poorly Mobilising Patients
CD34 x10
6
/l 2.1 12,1 15.2 12.5 4.8
In our recent experience of treatment of children and adults with CD34 x10
6
/kg 2.3 0.9
neuroblastoma, malignant lymphoma and MM at three different Plerixafor given ↑ ↑ ↑ ↑
Scandinavian institutions, six patients were remobilised using G-CSF
Patient 3 Leukocytes x10
9
/l 19.4 9.8 9.4
and plerixafor (see
CD34 x10
6
/l 0.0 2.0 1.9
Table 3) and another five patients were mobilised
using G-CSF + chemotherapy + plerixafor (see
CD34 x10
6
/kg
Table 4).
Plerixafor given ↑
Mobilisation Using Plerixafor in Addition to
Patient 4 Leukocytes x10
9
/l 23.4 16.1 34.1
CD34 x10
6
/l 4.7 8.1 10.2
Granulocyte Colony-stimulating Factor
CD34 x10
6
/kg 1.65 2.73
All of these six patients had once to twice previously failed to
Plerixafor given ↑
mobilise sufficient CD34
+
cells in a chemotherapy and G-CSF
Patient 5 Leukocytes x10
9
/l 14.8 30.9 29.7 29.7
mobilisation regimen. Four of the six patients were admitted to
CD34 x10
6
/l 6.4 36.5 29.9 24.9
apheresis and all four patients reached a sufficient peripheral stem CD34 x10
6
/kg 3.5 2.0 1.5
cell collection based on CD34
+
cell count. Plerixafor given ↑ ↑ ↑
Patient 6 Leukocytes x10
9
/l 32 39 27
In this pilot study the administration of plerixafor was highly variable at
CD34 x10
6
/l 24 14.7
each transplant centre, thus it is not possible to determine an optimal
CD34 x10
6
/kg 2.5 1.4
time for the initiation and end-point of plerixafor treatment when
Plerixafor given ↑ ↑
combined with G-CSF. In patients 1 and 3 the CD34
+
cell concentration
Numbers in bold indicate the number of cells harvested after the use of plerixafor.
in peripheral blood was not detectable at day four following G-CSF, and
only a low level was detected at day five. Administration of plerixafor leukocyte count and CD34
+
cell concentration in patients 10 and 11
in the evening of day five had no effect on mobilisation of both CD34 suggest that plerixafor treatment may have been started too early or
cells and leukocytes at day six. The possibility that the patients had not continued for long enough.
mobilised more efficiently as a result of additional days receiving
plerixafor cannot be excluded. Patients 2 and 5 confirm that the peak Summary and Conclusions
CD34
+
cell mobilisation with a combination of G-CSF and plerixafor Among patients selected for high-dose therapy with autologous
occurs consistently on days five and six. stem cell support, 15–20% are unable to mobilise and collect
sufficient numbers of stem cells to proceed to high-dose therapy.
In this pilot study of G-CSF + plerixafor we were able to successfully The use of G-CSF alone or with chemotherapy plus G-CSF appears
and predictably remobilise 60% of heavily pre-treated patients. No not to influence the percentage of mobilisation failures. From the
conclusions can be drawn with regard to plerixafor in combination data derived from the Scandinavian case series presented herein,
with G-CSF in patients with absolutely minimal CD34
+
cells. Our the type and amount of chemotherapy prior to stem cell
experience in patients 1 and 3 might suggest that at very low CD34
+
mobilisation can give some information on which patients can be
counts not all patients benefit from plerixafor treatment. The poor mobilisers. However, it is difficult to predict which of the
minimal threshold of CD34
+
cells in peripheral blood prior to the use individual patients will fall into the poor mobiliser group before
of plerixafor needs to be determined. mobilisation has started.
Mobilisation Using Plerixafor in The new mobilising agent plerixafor, which inhibits binding of SDF-1 to
Addition to Granulocyte Colony-stimulating CXCR-4, was shown in recent studies to successfully mobilise several
Factor + Chemotherapy poorly mobilising patients when used in combination with G-CSF.
54
In three out of five patients (9, 10 and 11), plerixafor was introduced Data from our institutions confirm that addition of plerixafor to G-CSF
into a G-CSF + chemotherapy regimen after a previously unsuccessful in patients who have already undergone at least one unsuccessful
mobilisation attempt. However, in two patients (7 and 8) plerixafor mobilisation attempt made it possible to mobilise sufficient numbers
was administered during the primary stem cell mobilisation using of CD34
+
cells to proceed to high-dose therapy.
G-CSF and chemotherapy to successfully prevent mobilisation failure.
Patients 7, 8 and 9 had successful collection in a single day following To our knowledge, little information exists on how plerixafor should be
one plerixafor administration. In patients 10 and 11, peripheral CD34
+
used in patients mobilised using chemotherapy and G-CSF. In our own
count was <2 cells/µl and subsequent apheresis did not result in experience, as shown in the case series presented, we were able to
minimal stem cell collection. As can be seen in Table 4, leukocyte successfully mobilise three out of five patients. Moreover, two of
rebound may provide additional guidance for the timing of plerixafor these three patients were given plerixafor during the first mobilisation
treatment and subsequent apheresis. Retrospectively, the very low attempt, whereas the third patient was remobilised.
EUROPEAN HAEMATOLOGY
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