thus poorly understood, and the impact of manipulations such 
as the use of peripheral blood versus bone marrow grafts, 
the use of hematopoietic growth factors before or after 
transplant or ex vivo, the use of ablative versus non- 
ablative conditioning regimens, and tumor cell purging or 
positive stem cell selection can not be effectively 
assessed . 1 In autologous transplantation, it is unknown if 
autologous marrow or peripheral blood cells simply provide a 
temporary bridge until endogenous marrow recovers, or if 
true viable stem cells are transplanted that completely and 
permanently repopulate the recipient. Retroviral marking 
provides a unique methodology for distinguishing cells 
arising from the autograft from those arising from 
recovering endogenous marrow. 
Following myeloablative therapy the combination of bone 
marrow plus peripheral blood stem cell (PBSC) infusions have 
led to more rapid hemopoietic reconstitution than observed 
with bone marrow support alone . 2 ' 3 The relative contribution 
of each to short or long term engraftment is unknown. In 
contrast, while many patients who receive PBSC autografts 
alone experience rapid hematologic recovery, a number endure 
incomplete, transient, or delayed reconstitution . 4 
Therefore, PBSC may provide a source of committed 
progenitors responsible for early, but often incomplete 
marrow regeneration, whereas bone marrow may contain 
pluripotent stem cells sufficient to achieve durable 
engraftment. In patients who receive PBSC alone, late 
recovery may be unrelated to the autograft and may instead 
result from endogenous recovery. 
By genetically marking PBSC and bone marrow, each with a 
unique retroviral marking vector, serial studies post- 
transplant may make it possible to determine their relative 
roles in hemopoietic reconstitution. If initial studies 
demonstrate the feasibility of marking these cells in vitro 
and being able to detect them post-transplant, the impact of 
a myriad of interventions could be assessed, including pre- 
harvest chemotherapy or growth factor therapy, in vitro 
expansion or purging of the harvested cells, and post- 
transplantation growth factor therapy. If permanent 
engraftment can be shown to occur with marked peripheral 
blood stem cells, then the use of this population for 
genetic therapy and even for allogeneic transplantation can 
be considered. 
The three clinical autologous transplantation protocols 
included in this amendment utilize different regimens prior 
to collection of bone marrow or peripheral blood cells, 
different conditioning regimens prior to transplant, and it 
is likely that in these three disease states hematopoiesis 
is very different at baseline. Both leukemic and non- 
Recombinant DNA Research, Volume 16 
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