Following myeloablative therapy autologous bone marrow plus 
peripheral blood stem cell (PBSC) infusions have led to 
rapid hemopoietic reconstitution in humans. The relative 
contribution of each to short or long term engraftment is 
unknown. Preliminary studies by Gianni 21 and Elias 20 using 
chemotherapy and GM-CSF-mobilized cells suggest that 
recovery with the combination is more rapid than with marrow 
transplantation alone. In one study the time to re- 
engraftment of platelets > 20,000/ul, neutrophils > 500/ul, 
and days to discharge from the hospital was shortened by 4, 
7, and 11 days, respectively 23 . There were no instances of 
delayed platelet count return. An unpublished study using G- 
CSF-mobilized peripheral blood cells in combination with 
bone marrow also found more rapid platelet and neutrophil 
reconstitution. (G. Morstyn, personal communication) In 
contrast, while many patients who receive PBSC autografts 
alone experience rapid hematologic recovery, a number endure 
incomplete, transient or delayed reconstitution. 64 
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. These hypotheses require 
further evaluation. 
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. 
4 . 0 PATIENT ELIGIBILITY 
4.1 < age 65 at' time of pretransplant evaluation. 
4.2 An established diagnosis of multiple myeloma, with a 
detectable serum or urine monoclonal paraprotein at the time 
of diagnosis or relapse. 
4.3 ECOG performance status of 0 or. .1 and a life-expectancy 
of greater than 3 months. 
4.4 Patients must be ineligible for standard allogeneic 
transplantation, based on age > 50, inability to identify a 
Recombinant DNA Research, Volume 16 
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