Circulating component of hematopoietic stem cells(HSC) markedly expand in the
recovery phase of chemotherapy or during administration of colony-stimulating factors(
CSF) and increasing number of clinical trials have been undergone to test the efficacy
of stem cell rescue operation after marrow ablative treatment used as an alternative to
autologous bone marrow transplantation(ABMT). The reasons for the popularity of
peripheral blood stem cell autotransplantation(PBSCT) include the ease of collection of
stem cells, more rapid engraftment, and the theoretical possibility that peripheral blood
stem cells (PBSC) contains fewer cancer cells compared to marrow. We showed that
harvesting PBSC for autografts In children with active cancers Is a safe and reliable
procedure with a low incidence of serious morbidity. In terms of preserving engraftment
potential, cryopreservation of PBSC by simplified uncontrolled-rate method is at least as
effective as the traditional controlled-rate freezing procedure with a programmed freezer.
After PBSCT, there is a sign nificant correlation between the number of infused
CFY-GM or CD34+ cells and the time to early phase granulocyte engraftments.
However, in our analysis, the number of LTCIC contained is the only ctor to have a
potential to predict stable phase hematopoietic reconstitution. Currently licensed CSFs
lack the potential to hasten platelet recovery after intense therapy, while use of
mobilized PBSC by CSF is the only immediate measure to ameliorate these problems,
accelerating both neutrophil and platelet recovery.
Use of mobilized PBSC offers opportunities to facilitate the use of more intensive
treatment regimens for high-risk childhood cancer, with an improved safety margin of
chemotherapy for malignant disorders. Our preliminary data with children with relapsed
acute lymphoblastic leukemia(ALL) suggest that application of PBSCT results Increase
In the salvage rate of patients, while avoiding toxicities of allogeneic BMT procedure.
On the other hand, the primary strategy of PBSCT for children still remaining in first
complete remission( CR) would be the improvement of therapeutic ratio by decreasing
the toxicities of intensified use of toxic anticancer drugs, without jeopardizing ultimate
cure rates. Prospective study has been underway to test its feasibility.
The role of PBSC other than use in transplantation setting continues to evolve. This
will also be used to support intermediate-dose conventional chemotherapy. With the use
of PBSC, repetitive cycles of high-dose chemotherapy can be delivered at veiny frequent
intervals and this will play a major role in the treatment of various solid tumors. Use of
PBSC eliminates the need for anesthesia. Development of effective procedure for
allogeneic transplantation with PBSC to expand the 5!em cell donor pool has been
underway. As the serum G-CSF level increases immediately following Infusion of PBSC
graft, exogenous application of G-CSF may have only a limited ability to further
enhance hematopoietic recovery after PBSCT. However, there might be a possibility that
early phase of engraftment speed after transplantation is significantly shortened or
period of pancytopenia can be eliminated, if ex vivo expanded compartment of commit)ed
progenitor cells by CSFs are Infused together with frozen-thawed PBSC. For this
purpose, establishment of effective purification Procedure of PBSC is urgently required,
which will also make the gene therapy Practical and feasible. The following Is currently
ongoing or proposed protocols regarding PBSCT in Japan.
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