autologous blood and marrow transplantation - Blog Science ...

436 Chapter 7: Solid Tumors
INTRODUCTION
Autologous stem cell transplantation (autoSCT) permits the administration of
high-dose chemoradiotherapy followed by the infusion of the patient's own
hematopoietic cells, previously collected and cryopreserved. 1
AutoSCT may be the
best treatment option for patients with acute leukemia in first remission and
intermediate- or high-grade non-Hodgkin's lymphoma. 23
This therapeutic
approach may also be the treatment of choice for patients with acute leukemia,
Hodgkin's disease and non-Hodgkin's lymphoma at first relapse. 4
Recent reports
also indicate that autoSCT may be an effective treatment for patients with a number
of different types of solid tumors, including breast cancer, gonadal cancer, and
neuroblastoma. 5
For several years, marrow-derived cells have represented the main source of
hematopoietic reconstituting cells. 6
More recently, mobilized peripheral blood
progenitor cells (PBPC) have been increasingly used to reconstitute hematopoiesis
in patients undergoing high-dose chemoradiotherapy. 7
PBPC collections comprise
a heterogeneous population containing both committed progenitors and pluripotent
stem cells and can be harvested 7) in steady state, 2) after chemotherapeutic
conditioning, 3) after growth factor priming, or 4) after both chemotherapeutic
conditioning and growth factor priming. 8
G-CSF, alone or in combination with
chemotherapy, is widely used for stem cell mobilization. The availability of PBPC
has opened new therapeutic perspectives to alleviate the severe toxicity related to
prolonged myelosuppression 9
and is associated with a number of clinical benefits
including a reduction of platelet transfusions and shorter hospital stay. 9
In addition,
the availability of large numbers of mobilized hematopoietic stem and progenitor
cells that can be easily collected through leukapheresis allows extensive manipulations
of the grafts, including positive and negative selection as well as the
possibility to exploit these cells as vehicles for gene therapy strategies. 10
The development of mobilization protocols aimed at improving the quantity and
quality of collected PBPC represents an area of active investigation. In fact, 7)
optimal regimens for PBPC mobilization are not yet established; 2) there is a wide
individual variability in mobilization yields (poor yields being achieved in 5-15% of
normal donors) 11
; 3) with currently used mobilization protocols, patients who have
received extensive prior chemotherapy or radiotherapy may be poor mobilizers; and
4) there is an expanding use of high-dose sequential chemotherapy strategies
requiring the collection of large numbers of CD34 +
cells. Currently, new approaches
to improve PBPC mobilization include combinations of G-CSF or granulocytemacrophage
(GM)-CSF with other cytokines such as interleukin (IL)-3, stem cell
factor (SCF), Flt3 ligand, and macrophage inflammatory protein let (MlP-la). 12-17
Amifostine (WR-2721) is a phosphorylated aminothiol compound that
increases the selectivity of anticancer drugs for neoplastic cells, protects normal