HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
P, 
I 
i 
We will institute a screening program for evidence of malignancies in patients ' 
receiving HCT and marker genes. Unfortunately, clinical methods for detecting i 
malignancies are limited. We will perform serial ultrasound examinations and AFP .»i 
determinations to screen for malignancies in the liver. We will be particularly attuned 
to the possibility of leukemia or lymphomas, will perform regular hematological analysis ^1 
(CBC) , and will obtain bone marrow aspirates at intervals following transplantation L 
which will be tested for evidence of retroviral integrations and any evidence of S| 
abnormal differentiation. CEA and AFP which are commonly used markers of malignancies :'| 
may be expected to be elevated following hepatic disease and transplantation, but will > 
be followed for unexpected fluctuations. Immunoglobulin electrophoresis may be useful )t': 
in identifying monoclonal increases which would be indicative of a expanding clone of • 
EBV transformed E cells. Regular radiological imaging is not clinically indicated since i 
there is no reasons to expect that the theoretical risk of malignancies from exposure 
to the vector is higher than the determined risk of unnecessary diagnostic radiation. , 
1 , • 
If malignancies are observed, samples will be analyzed for evidence of recombinant I 
retroviral insertions as well common carcinogenic factors or oncogenic viruses. If -[I 
retroviral integrations are observed, the clonal nature of the malignant pool will be j 
characterized in an attempt to determine whether there was credible evidence for a ' ■ 
retroviral cause of any malignancy. 
H. Long-term follow-up. 
a regular basis in the context of future developments in somatic gene therapy, 
routine evaluations will include; 
.1 1 
As described above, we believe that one of the most important ethical issue in the ®’ 
present protocol is the quality of clinical responsibility and long-term follow-up. We 
will address the need for follow-up in several ways. 
1. Informed Consent. Patients will be strongly advised of the importance of 
participating in long-term follow-up as part of the informed consent. They will also 
be informed of the importance that the Recombinant DNA Advisory Committee ascribes to 
follow-up by reading the statement in the "Points To Consider ... " . 
2. Health surveillance - the role of TCH. Subjects and their families will be followed 
on a continuing basis both by the investigators at TCH and by their local primary health 
care provider. As long as acute care is required, it is likely that most of the primary 
care will be provided at the TCH. We will strongly recommend to families that they 
participate in evaluations at regular intervals of not more than six months, regardless 
of their clinical course. The frequency of these evaluations will be reconsidered on 
These t 
I. ' 
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Recombinant DNA Research, Volume 14 
