Recombinant DNA Advisory Committee - 06/1-2/92 
Dr. Walters stated that the investigators should define the control groups more clearly in 
the revised protocol. What forms of chemotherapy will be available these groups of 
patients? 
The motion to defer approval of the syngeneic protocol passed by a vote of 20 in favor, 0 
opposed, and no abstentions. 
VII. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING 
A HUMAN GENE TRANSFER PROTOCOL ENTITLED USE OF TWO RETROVIRAL 
MARKERS TO TEST RELATIVE CONTRIBUTION OF MARROW AND PERIPHERAL 
BLOOD AUTOLOGOUS CELLS TO RECOVERY AFTER PREPARATIVE 
THERAPY I DR. DEISSEROTH: 
Review-Dr. Doi 
Dr. Murray called on Dr. Doi to present his review. Dr. Doi presented an overview of 
the protocol submitted by Dr. Albert Deisseroth of MD Anderson Cancer Center, 
University of Texas, Houston, Texas. Dr. Doi stated that the proposed objective of the 
protocol is to determine if leukemia relapse following autologous bone marrow and 
peripheral blood stem cell transplantation is a result of: (1) leukemic blast cells 
remaining in the systemic circulation after preparative therapy, or (2) blastic leukemia 
cells remaining in the autologous peripheral blood stem cells and marrow that is used for 
restoration of marrow function. 
Dr. Doi noted that the protocol is designed to determine the relative contribution to 
relapse of peripheral blood versus hematopoietic cells after transplantation. Chronic 
myelogenous leukemia (CML) patients will be tested after reinduction of second chronic 
phase or cytogenetic remission after accelerated phase or blast crisis. Two retroviral 
vectors containing genes coding for neomycin resistance, LNL6 and GINa, will be used 
to mark the patient's autologous bone marrow cells and peripheral blood cells, 
respectively. Patients will be screened by PCR for these two genes at the time of 
relapse. 
Dr. Doi explained that PCR analysis will also be used to determine whether the marked 
blast cells are normal or leukemic by testing for the Philadelphia chromosome marker, 
BCR-abl mRNA. Morphological studies and fluorescent in situ hybridization will be 
used to measure the level of leukemic cells present among the autologous cells used for 
transplantation. If the neomycin resistance marker gene is detected in patient's blast 
cells, relapse will be indicated by the transplanted autologous bone marrow and/or 
peripheral blood. Conversely, if no marker is detected, relapse from systemic disease 
will be indicated. 
Recombinant DNA Research, Volume 15 
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