NON-TECHNICAL ABSTRACT 
High-Dose Chemotherapy and Autologous Bone Marrow plus Peripheral Blood Stem Cell 
Transplantation for Patients with Lymphoma or Metastatic Breast Cancer: Use of Marker 
Genes to Investigate the Biology of Hematopoietic Reconstitution in Adults. 
PRINCIPAL INVESTIGATOR: Dan Douer, MD 
This protocol is intended for patients with breast cancer or lymphoma who will be treated by 
autologous bone marrow transplantation (BMT) to restore their bone marrow function that has 
been previously damaged by high doses of chemotherapy drugs. The bone marrow is the site 
where all blood cells are produced from cells that we call "stem-cells". Because the high doses 
of chemotherapy will destroy these normal blood producing cells (stem-cells), transplantation of 
the previously collected bone marrow (which contains stem-cells) is necessary. We know that 
the blood also contains a few stem cells, which can be collected then transplanted together with 
the bone marrow cells. It is believed that by adding blood stem cells to the bone marrow cells, 
the recovery of bone marrow function after the transplantation is faster. However, we do not 
know if these circulating blood stem cells are different from the bone marrow stem cells, or if they 
are also capable of permanently renewing the bone marrow function. We also do not know if a 
few invisible cancer cells may be still present in the transplanted bone marrow or blood and 
whether they contribute differently to recurrence of cancer after being infused back into the 
patient. 
To answer these questions, we will insert a gene into some of the bone marrow and a slightly 
different gene into some of the blood cells. A special laboratory technique will be used to put the 
genes into a portion of the bone marrow and a portion of the blood which were previously 
collected. These treated bone marrow and blood cells are referred to as "marked" cells. By 
inserting these particular genes into the cells, we will be able to distinguish the marked cells from 
all other cells in the body. If any of the blood cells and marrow cells that return after the 
transplantation contain the cells that are marked by the gene, we would be able to follow these 
markers over a long period of time. We then would know if the blood stem cells or bone marrow 
stem cells were responsible for permanent marrow function after the transplantation. In addition, 
if the cancer re-occurs, and one or both of the genes is present in the recurring tumor, we may 
be able to determine if invisible tumor cells were actually present in the bone marrow or blood, 
perhaps contributing to the relapse of cancer after transplantation. In this clinical trial, 1 0 patients 
with lymphoma or breast cancer will be studied. 
The introduction of these genes would have no treatment benefit to the patient but the results 
may lead to a better understanding as to how the bone marrow and blood stem-cells recover after 
transplantation and also may help to plan better ways to improve the safety and usefulness of this 
procedure. 
No side effects have been seen in animals or any person treated thus far with these marker 
genes. Consequently, for the several patients who have already received these genes, no side 
effects ("toxicity") have been observed. 
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Recombinant DNA Research, Volume 20 
