VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

PROCESSING OF STEM CELLS FOR TRANSPLANTATION
Subhash C. Gulati, M.D., Ph. D., Patrick Stiff, M.D., Jeffrey Gaynor, Ph.D.
and Luis Acaba, M.D.
Autologous Bone Marrow Transplant Team, Department Of Medicine and
Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New
York, NY 10021, USA and Loyola University, Maywood, Illinois, USA
ABSTRACT
The success of autologous stem cell transplantation using bone marrow or
peripheral blood stem cells depends not only on in vivo irradication of the disease
by cytotoxic therapy but also on complete hematopoietic engraftment with
no risk of relapse from the infused cells. Various methods are available for removing
(purging) such contaminants. Purging techniques were developed by
use of various in vitro models utilizing cell lines and fresh cancer cells. Once effective
conditions were developed, they were advanced onto clinical trials. Various
approaches for purging and subsequently freezing stem cells have been
used. Subgroups of leukemia and lymphoma patients have now been shown to
clinically benefit by the use of purged, cryopreserved stem cells. Emphasis is
now being placed on utilizing the information already obtained by the pre-clinical
investigators on designing better clinical trials.
INTRODUCTION
High dose cytotoxic therapy with hematopoietic stem cell (HSC) rescue is
now the treatment of choice for various malignancies. It has improved the long
term disease free survival (LT-DFS) of patients with lymphoma, Hodgkin's disease
and acute myeloblastic leukemia 13
. Many factors (Table 1) affect the quality
and quantity of hematopoietic stem cells obtained from the bone marrow or peripheral
blood stem cells (PBSC). Improvements in the methods of HSC harvest
and purging will result in better hematopoietic engraftment and lower relapse
rate.
IS HEMATOPOIETIC STEM CELL RESCUE REQUIRED AFTER CYTOTOXIC
THERAPY?
We now have substantial understanding about how much dose escalation is
possible without any hematopoietic stem cell support, especially with the use of
hematopoietic growth factor(s). If good therapeutic benefit can be obtained with
conventional or intermediate dose therapy, the patients need not be subjected to
the risks associated with more intensive treatment followed by stem cell rescue
(relapse from infused cancer cells, poor hematopoietic engraftment, cost, etc.).
For drug(s) under phase I evaluation, emphasis can be placed on deciding this
threshold (maximum tolerable dose with growth factors [no HSC rescue] and if
needed, with HSC rescue) rather early in clinical trials 2
.
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 145