Gene Therapy for Meningeal Carcinomatosis 
5.3 Post-Treatment Evaluations 
5.31 Complete Neurological and Physical Examination: Complete neurological and 
physical examinations will be done by study physicians at each follow-up evaluation 
5.32 Blood Chemistries and Hematology : Complete blood count (CBC), differential, 
platelets, prothrombin time, partial thromboplastin time, uric acid, calcium, phosphorus, 
magnesium, amylase, triglycerides, transaminases (SGOT, SGPT), alkaline phosphatase, LDH, 
total bilirubin, BUN, creatinine, albumin, total protein, electrolytes, glucose will be done at regular 
follow-up intervals. 
5.33 CSF Sampling : CSF samples from lumbar puncture and Ommaya reservoir 
aspiration will be obtained at predetermined follow-up intervals for cell count, glucose, total 
protein, cytology, appropriate marker studies, and vector titer. 
5.34 MRI Scans : Gadolinium-enhanced MRI scans of the brain and spinal cord will be 
done at each follow-up evaluation. 
5.4 Autopsy Request 
All participants in the study will be informed that an autopsy will be requested to determine 
the extent of gene transfer into important organs such as marrow, liver, and spleen. 
5.5 Considerations/Evaluations Upon Premature Withdrawal 
Patients who are discontinued or withdraw before completing the study, but have 
completed at least 1 cycle of therapy will be asked to return to die clinic to be evaluated according 
to Section 5.3. 
5.6 Retreatment Criteria : 
If initial response to the treatment was demonstrated, but there is residual disease or the 
leptomeningeal carcinomatosis recurs, repeat retreatment will be considered. 
6.0 Treatment Modification and Discontinuation According to 
Level of Toxicity 
The Table for Grading Severity of Adverse Experience (Appendix VI) will be used to 
achieve consistency in response to drug/treatment toxicities. Toxicides will be graded on a 1 - 4 
grading scale. If a toxicity is experienced, the treatment level or dose will be modified as outlined 
below according the grade of toxicity observed. 
6.1 Treatment Modification and General Management of Toxicides 
For Grades 1, 2, and 3 toxicity symptomatic treatment with careful monitoring of the 
patients clinical condition will be performed. Such symptomatic treatment may consist of CSF 
diversion for hydrocephalus as discussed previously in section 3.32. Medical management of 
chemical meningitis using medications routinely used in neurosurgical practice for symptomatic 
relief is discussed below (6.11). 
Development of Grade 4 toxicity which responds to therapy will be treated symptomatically 
as above. Any Grade 4 toxicity which is unresponsive to therapy will necessitate modification in 
the dose of vector-producer cells to the number of cells administered at a previous phase for the 
next patient. 
Recombinant DNA Research, Volume 18 
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