C. HESDORFFER 4/93 
2) Has a small risk of viral infection and an even smaller risk 
of developing a new cancer. The risk is no greater than that of 
conventional chemotherapy, and no cases of retroviral infection 
or cancer have occurred in previous clinical trials; 
3) Eventually might allow their bone marrow to be more resistant 
to the effect of chemotherapeutic agents enabling further 
chemotherapy to be administered without repeated ABMT and with 
less marrow side effects; and 4) May eventually lead to new 
therapy for a variety of disease states. A consent form 
indicating these considerations is included at the end of this 
section as part of the protocol. 
D. Potential Risks : 
The major potential risk of this procedure is that the 
transfer of retroviruses into the bone marrow cells of patients 
will alter the normal function of repopulating bone marrow. To 
date, no such untoward effects have been demonstrated when genes 
are introduced into or humans (76-78) by retroviruses. 
Especially important in the safety of this procedure is that no 
intact retroviruses capable of producing productive retroviral 
infection are administered. The packaging lines used in the 
proposed experiments has been demonstrated to be safe in animal 
studies (16,17). Safety of the MDR transducing retroviral 
producer line A12M1 will be assessed in transduced human bone 
marrow cells; 1) In immunodef icient mice given these cells; 
2) In fresh marrow cells using coculture with Mus-dunni cells 
and naive 3T3 cells and subsequent testing of supernatants for 
reverse transcriptase and MDR by PCR; and 3) Exposing these 
supernatants to PG4 cells and performing the S+L assay. 
E . Confidentiality : 
In addition to the description of the cautionary 
measures indicated in #4 above, confidentiality of the identity 
of the patients will be maintained by the physicians involved in 
the protocols. In the event of adverse effects, appropriate 
medical attention will be administered immediately. These 
subjects will be carefully monitored by repeated blood count 
analysis and intermittent bone marrow collection to determine the 
safety and efficacy of retroviral gene transfer. 
F. Risk/Benefit Ratio ; 
The risks in these experiments appear to be quite low 
on the basis of other retroviral gene transfer experiments 
already reported from the NIH and currently underway (76-78) . 
The anticipated benefit to the subjects is not significant in the 
short run; in the long run, if successful, the use of the MDR 
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Recombinant DNA Research, Volume 18 
