Kvalheim_EUHaemotology_EU Haematology 09/03/2010 09:12 Page 24
Transplantation
The Use of Plerixafor for Peripheral Blood Stem Cell Mobilisation
Reduces the Frequency of Mobilisation Failure in Patients
Planned to Undergo Autologous Transplantation
Dag Josefsen,
1
Catherine Rechnitzer,
2
Katriina Parto
3
and Gunnar Kvalheim
1
1. Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital;
2. Department of Paediatrics, Rigshospitalet, Copenhagen University Hospital; 3. Paediatric Haematology, Tampere University Hospital
Abstract
High-dose chemotherapy with or without radiation followed by autologous haematopoietic stem cell transplantation (auto-HSCT) is now the
standard of care for patients with chemosensitive relapsed aggressive non-Hodgkin’s lymphoma (NHL), chemosensitive relapsed Hodgkin’s
disease (HD) and multiple myeloma (MM). Autologous haematopoietic stem cells also provide haematopoietic support after the administration
of high-dose chemotherapy in relapsed NHL and MM. However, certain patients fail to mobilise a sufficient number of haematopoietic stem cells
using standard cytokine-assisted mobilisation strategies. Recently, plerixafor, a novel bicyclam capable of specifically and reversibly binding to
the CXCR4 receptor on haematopoietic stem cells, has been granted European approval, in combination with granulocyte colony-stimulating
factor, for the enhancement of haematopoietic stem cell mobilisation to the peripheral blood for collection and subsequent autotransplantation
in poorly mobilising lymphoma and MM patients. In this article the authors present their initial experience with plerixafor in a case series at their
own institutions in Scandinavia.
Keywords
Autologous, stem cell, mobilisation, granulocyte colony-stimulating factor (G-CSF), autologous stem cell transplantation (auto-SCT), peripheral
blood stem cells (PBSCs), chemotherapy, plerixafor
Disclosure: The authors have no conflicts of interest to declare.
Received: 19 February 2010 Accepted: 5 March 2010 Citation: European Haematology, 2010;4:24–9
Correspondence: Gunnar Kvalheim, Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway.
E:
gunnar.kvalheim@medisin.uio.no
Autologous haematopoietic stem cell transplantation (auto-HSCT) has attaching to the bone marrow stroma.
14
These discoveries led to the
been used successfully in certain forms of haematological cancer and use of recombinant cytokines in mobilisation regimens, either alone
is now the standard of care for relapsed non-Hodgkin’s lymphoma or following chemotherapy, to enhance PBSC collection by apheresis.
(NHL) and for subgroups of patients with multiple myeloma (MM).
1–3
This review will discuss current approaches, issues and developments
Auto-HSCT also provides haematopoietic support after the in reducing failure to collect sufficient PBSCs in auto-HSCT in NHL and
administration of high-dose chemotherapy in relapsed NHL and MM. MM. The authors also present their initial experience in a case series
Several clinical trials comparing conventional chemotherapy with of patients treated at their own institutions in Scandinavia with
high-dose chemotherapy and auto-HSCT have shown improved plerixafor, a new agent for stem cell mobilisation.
outcomes in patients who received auto-HSCT.
4–6
While bone-marrow-
derived cells were originally the main source of stem cells in Current Haematopoietic Stem Cell
autologous transplants, they have largely been replaced by peripheral Mobilisation Strategies
blood stem cells (PBSCs). Clinical trials have demonstrated that PBSCs The number of harvested PBSCs is determined by several factors,
offer several advantages over bone-marrow-derived cells, such as including disease status, prior treatment, patient age, gender and
more rapid engraftment, faster recovery times and reduced need for previous mobilisation attempts.
15–17
The efficiency of stem cell
transfusion support.
7–10
However, circulating levels of haematopoietic mobilisation and collection is of primary importance since it has a
stem cells, as measured by the surrogate marker CD34
+
, which is major influence on the success of the auto-HSCT.
18,19
Studies suggest
expressed on haematopoietic stem and progenitor cells, are relativity that for successful haematopoietic recovery and sustained
low. Early investigations showed that stem cells could be harvested engraftment a minimum infusion of ≥2.0x10
6
CD34
+
cells/kg
from the peripheral blood during the recovery phase after bodyweight is required.
14,20,21
Furthermore, mobilisation and infusions
myelosuppressive chemotherapy
11
and that cytokines, such as ≥5x10
6
CD34
+
cells/kg bodyweight are associated with more rapid
granulocyte colony-stimulating factor (G-CSF; filgrastim) and platelet recovery and overall survival.
22–25
granulocyte macrophage colony-stimulating factor (GM-CSF;
sargramostim) could improve stem cell mobilisation.
12
G-CSF Unfortunately, for some patients, the current mobilisation regimens
promotes the proliferation and differentiation of HSC
13
while are associated with mobilisation failure rates of up to 30%.
26–30
promoting the release of enzymes that prevent these cells from Unsuccessful initial stem cell mobilisation can increase costs due to
24
© TOUCH BRIEFINGS 2010
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