Recombinant DNA Advisoiy Committee - 5/30-31/91 
Dr. McGarrity noted that because of a mix-up in scheduling consideration of Dr. Brenner's 
protocol would be delayed and asked Dr. Deisseroth to present his proposal to begin the 
morning session. 
X. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A 
HUMAN GENE TRANSFER PROTOCOL ENTITLED AUTOLOGOUS TRANSPLANTA- 
TION FOR CHRONIC MYELOGENOUS LEUKEMIA: RETROVIRAL MARKING TO 
DISCRIMINATE BETWEEN RELAPSES ARISING FROM RESIDUAL SYSTEM DISEASE 
VERSUS RESIDUAL CONTAMINATION OF AUTOLOGOUS MARROW: 
Dr. Deisseroth noted that chronic myelogenous leukemia was a disease in which a very 
indolent initial presentation evolves into fulminant acute leukemia in which the patients die 
of bleeding and infection. He said that currently there are three therapeutic approaches to 
the treatment of this disease, two of which involve bone marrow transplantation (BMT). He 
noted that the protocol will attempt to control the last phase of the diseased where patients 
face a 100 percent threat of mortality due to the fulminant acute leukemia and where 
currently intensive drug therapy is utilized which requires hematopoietic reconstitution by 
means of either an autologous or allogeneic bone marrow transplant. He said the protocol 
was aimed at trying to determine, in relapse, whether the relapse is arising from residually 
contaminated autologous marrow or residual systemic disease in the patient. 
Dr. Deisseroth said that the dilemma in trying to improve therapy to prevent relapse is that 
if they are to increase the radiation and chemotherapy to eradicate residual systemic disease 
there would be increased mortality and if they try to increase the methods used to clean up 
the marrow this could result in failure of engraftment as well as delayed recovery. 
He said the current approach is to use conventional dose combination chemotherapy to 
reduce the level of contamination of leukemic cells in the marrow and then to collect the 
marrow at this state of minimal disease and infuse the autologous marrow. However, total 
body irradiation and combination chemotherapy is insufficient to eradicate all of the systemic 
disease and therefore this protocol would be aimed at using the LNL6 marking vector to allow 
them to discriminate between a relapse caused by inadequate preparative therapy or 
inadequate purging of the marrow. He said what was envisioned was that after the autologous 
marrow was collected it would be incubated, in vitro, with the LNL6 marking vector and 
frozen. The major question is whether it is possible to introduce the marking vector into 
enough cells with leukemic blasts so that after engraftment there would be a substantial 
probability if relapse occurs from the marrow that these blasts will possess the marking vector. 
If the marking vector genes are detectable in these blasts then one could conclude that the 
marrow was inadequately prepared and one should focus on cleaning up the marrow further, 
and in contrast if no evidence of the retroviral trans genome was found in the leukemic blasts 
at the time of relapse one could perhaps focus more on the systemic disease. 
Dr. Deisseroth said they had presented data at the HGTS to show that they were able to mark 
the chronic phase chronic myelogenous leukemia (CML) marrow by incubating it with the neo 
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Recombinant DNA Research, Volume 14 
