advances to grade 4 toxicity, G-CSF will be 
discontinued and the patient will not re-start the 
medication. The patient will continue to have 
apheresis as if G-CSF were administered for the 
current cycle only. The patient will receive no 
further G-CSF, and therefore no further cycles of 
peripheral stem cell harvest will be attempted 
under this protocol. 
► For Grade 3 toxicity not related to G-CSF, the 
investigators and sponsor will discuss the various 
options available. The appropriate action 
relative to the patient with a Grade 3 toxicity as 
well as a discussion of enrolling other patients 
will be addressed. Since no toxicities have been 
seen in other gene transfer protocols, precedence 
for the appropriate action is not available and 
will need to be decided on a case-by-case basis. 
6.11 Management of Specific Toxicities 
Adverse reactions to apheresis ; Reactions are 
rare, and include anxiety, vasovagal reactions, 
and cutaneous paresthesias related to citrate - 
induced hypocalcemia. Sedation, volume repletion, 
and slowing of the infusion will correct these 
problems. Bleeding and infection at the line 
insertion site are potential complications of 
apheresis catheter placement. 
6 . 2 Symptomatic Therapy for Toxicity 
Symptomatic therapy such as analgesics or other helpful 
therapy may be administered if deemed necessary by the 
participating investigators. All medications 
administered will be recorded in the appropriate Case 
Report Form. 
7.0 CRITERIA FOR DISCONTINUATION OF STUDY PATIENTS 
7 . 1 Criteria for Treatment Discontinuation 
Participation in this study can be discontinued for any 
of the following reasons listed below: 
o At the Patient's request: Any patient who wishes 
to withdraw from the study may do so but will be 
counselled that long-term follow-up for the 
effects of gene therapy are strongly desired by 
the medical facility and federal regulatory 
groups . 
o A major, unexpected, or life-threatening toxicity 
requiring that treatment be discontinued 
o Generalized impairment or mental incompetence 
which would render the patient unable to 
understand his/her participation in the study, 
o If, in the Investigator's medical judgment, 
further participation would be injurious to the 
subject's health or well-being, 
o Administrative reasons, such as subject non- 
compliance or a major protocol violation, 
o Pregnancy 
An explanation will be recorded for any patient that is 
taken off treatment and the appropriate Case Report 
Form completed . 
Recombinant DNA Research, Volume 19 
[565] 
