Recombinant DMA Advisory Committee - 5/30-31/91 
by saying that there is no method currently that will allow investigators to know that the 
marrow is going to cause a relapse and all that can be said is that some marrows are likely 
to be contaminated. However, it is impossible to know whether those contaminating cells are 
clonogenic or not, or whether they are end-stage cells incapable of proliferation. He noted 
that there is an in vitro technique under development which will allow investigators to 
determine whether the patient will develop a marked relapse, and if this becomes available 
the investigators will be able to avoid carrying out the marking of the cells. This was the 
premise underlying the stopping rule which had been mentioned previously. 
Dr. Leventhal said that at present the in vitro cultures were state-of-the-art for the treatment 
of neuroblastoma, however the results are not received until after the marrow is reinfused. 
She underlined that this was not any different than standard experimental clinical practice in 
these patients at this time. 
In response to Dr. Atlas' question about the pre-treatment studies. Dr. Brenner said that these 
tests would help investigators to assess risk and if such conditions were found the patient 
would be notified that they may be at increased risk by undergoing the protocol. He noted 
that if HIV were found the patient would not be transplanted because of the difficulty 
involved with doing a transplant on an immunosuppressed host. He said he would add a 
phrase in the informed consent document to state: "We will discuss these altered risks with 
you (your child)." 
He noted, in response to the question referring to the language difficulty in the assent and 
consent forms, that the Medical Editing Department had revised these forms to conform with 
the reading comprehension level of 8-10 year olds. He did say he agreed that some of the 
language was still very complex and agreed to have them reassess this. He also said he would 
try to separate the experimental and therapeutic benefits although some of these children 
were expected to go on to participate in subsequent protocols. He said that at least they 
would add in a sentence noting that the gene marking may not work, as well as some note of 
the fact that antibiotic therapy may require some adjustment. He said the word "cure" had 
been purposely put into the document because a proportion of patients do become long-term 
survivors and are apparently cured. He said he would modify this wording but he felt that 
there was a hope that at least some of the patients would be long-term survivors and for all 
intent and purposes cured of their neuroblastoma. 
Dr. Brenner said that the question of who decides what is necessary care is a part of a list of 
10 phrases and questions derived from an NIH document and which had appeared in all 
protocols developed by his institution. He said that as a rule the provision of care was 
liberally administered and that if there were any question or doubt about the care being given 
to any patient that the investigators would wish to see the patients and will have an 
opportunity since there is a plan to follow these patients up for a long period. 
Dr. Brenner said that animal data was unclear as to whether neuroblastoma was the result of 
a single cell or many cells and he said this was also the case in human cell lines. He noted 
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