eradicate all clonogenic tumor cells. The high frequency of 
relapse after allogeneic transplantation supports this 
hypothesis. There may be a population of non-cycling tumor 
cells, especially during clinical "plateau phase", that are 
insensitive to primarily cell-cycle specific chemotherapy 
and radiotherapy. These cells may lay dormant for long 
periods after therapy, then be released by some change in 
microenvironment. It is also possible that patients 
initially revert back to a pre-myeloma state (i.e. a benign 
monoclonal gammopathy) characterized by persistence of a low 
level M-component but no other characteristics of myeloma, 
then stochastically again acquire a second mutation that may 
be required for unchecked neoplastic proliferation . 19 
Retroviral gene marking protocols approved by the 
Recombinant DNA Advisory Committee (RAC) and now in progress 
for neuroblastoma, acute myelogenous leukemia and chronic 
myelogenous leukemia offer a potential approach to 
investigate whether or not reinfused marrow act as a 
reservoir for viable clonogenic tumor cells. We will 
propose a protocol amendment in the future to apply this 
gene marking approach to myeloma. This is an important 
issue, because marrow purging by immunotoxins , cytotoxic 
agents, monoclonal antibodies or physicochemical separation 
may delay engraftment, thus increasing the morbidity and 
mortality of transplantation . 86 Animal and preclinical 
studies have shown that these methods all reduce 
contamination of normal marrow mixed with tumorigenic 
immortalized cells, but no purging protocol has yet been 
shown to convincingly impact on relapse rate or survival 
when naturally-occurring tumor-infiltrated marrow is purged 
prior to transplantation. The resolution of this issue will 
help focus further protocols, because at present much energy 
and time is being devoted to developing purging techniques 
for myeloma and other marrow-infiltrating malignancies. 
3.5 BIOLOGY OF HEMATOPOIETIC RECONSTITUTION AFTER 
TRANSPLANTATION 
Unlike allogeneic transplantation, where genetic markers can 
be used to definitively identify donor versus recipient 
hematopoietic cells, the biology of hematopoiesis following 
autologous transplantation is poorly understood. It is 
unknown if harvested and stored 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. Cells originating from progenitors or stem cells 
in the autograft can not be distinguished from cells 
•originating from residual progenitor • or stem cells surviving 
^ conditioning therapy. 
Recombinant DNA Research, Volume 16 
