Autologous Bone Marrow Transplantation - Blog Science Connections

630 Peripheral Stem Cell Transplantation
It is well known that circulating progenitor cells in humans are increased
during recovery from myelosuppressive chemotherapy (25). Large numbers
of CFCi-GM circulate also in very early remission after induction therapy for
AML (26-29). The CFCI-GM compartment in these patients is preferentially
expanded 10-25 fold, but CFCI-GEMM are increased only about three-fold
(13,28). In all centers performing ABSCT for leukemia or lymphoma (9-17;
see also both chapters by Reiffers et al. in this volume), hematopoietic
progenitor and stem cells were collected during the recovery phase after
various chemotherapy regimens.
Mobilizaton of progenitor cells, however, appears to depend very much
on the patients' pretreatment. In our series of heavily pretreated patients with
lymphoma we could not observe an expansion of the circulating progenitor
cell pool after a course of cyclophosphamide (15 mg/kg/b.w. x 4 days), a
finding not previously reported in humans. Heavy and prolonged cytotoxic
treatment seems to exhaust the mobilizable progenitor cell pool. This is in
agreement with canine data (30-34). Consequently, circulating progenitors
should be collected as early as possible after diagnosis or after achieving first
complete remission.
Besides cytotoxic treatment, which causes subsequent expansion of the
peripheral blood stem cell pool, a number of other approaches designed to
increase the peripheral blood stem cell concentration have been reported.
The administration of endotoxin (35,36), pyran copolymer (37) and related
agents, or low-molecular-weight dextran sulfate has been studied in animal
models, but these compounds have not yet been approved for clinical use.
Other factors have not yet produced conclusive or reproducible results; they
include exercise and the use of corticosteroids or activators of endogenous
steroid production (ACTH, prednisone, hydrocortisone) to mobilize peripheral
stem cells to overshoot after transient chemotherapy-induced myelosuppression
(40-42). Recombinant human granulocyte-macrophage colonystimulating
factor may eventually prove useful.
Transplantation of circulating stem cells may have advantages over
marrow-derived stem cells. For example, in patients at risk for general
anesthesia, continuous-flow apheresis offers an alternative and safe way to
harvest stem cells. Harvesting, processing, and freezing blood stem cells is
simple and can be done in blood banks, like the handling of any other blood
component. Furthermore, stem cell harvesting is feasible when the marrow
collection site has been damaged by previous radiotherapy or tumor
involvement.
A further factor favoring ABSCT is that hematopoietic reconstitution
after myeloablative treatment and ABSCT seems to be more rapid for the
WBC line, and therefore the aplasia-related risks in the early posttransplantation
period are lowered, provided sufficient numbers of stem cells are
transplanted. And finally, the ratio between normal hematopoietic stem cells
and clonogenic tumor cells in the peripheral blood of patients with malignant