Search

Between 1984 and 1993, monoclonal antibodies (MAbs) radiolabelled with 131I were administered into the CSF of 52 patients with neoplastic meningitis (meningosis) with progressive disease despite active conventional therapy. Selection of MAbs was based on immunoreactivity with patients' tumour and lack of binding to normal central nervous system (CNS) tissue.

Between 1984 and 1993, monoclonal antibodies (MAbs) radiolabelled with (131)I were administered into the CSF of 52 patients with neoplastic meningitis (meningosis) with progressive disease despite active conventional therapy. Selection of MAbs was based on immunoreactivity with patients' tumour and lack of binding to normal central nervous system (CNS) tissue. Following full clinical assessment and neuro-imaging which included isotope flow study of CSF pathways, (131)I-MAb was administered via a ventricular access device, lumbar catheter or both. Radioisotope activity varied from 25 mCi to 160 mCi in adults. Dose escalation was carried out and some patients received multiple doses. Distribution of (131)I-MAb and clearance kinetics were derived from serial scintigraphy and CSF/blood sampling. Evidence of localisation to tumour was frequently observed. Toxicity was minimal and easily treated, although one death occurred, possibly due to a seizure. The best results were obtained in primitive neuroectodermal tumour (n=22), where 53% of evaluable cases had responses and 11% had stable disease, adults responding better than children. Three exceptional survivals have been recorded; one patient leads a normal life at 10 years 11 months, one case is alive and normal at 3 years, 2 months. A third case survived in good condition for 8 years. The mean survival of responders was 39 months and non-responders 4 months. In the total series, 50% of patients survived for at least one year with 2 long term survivors. CSF therapy with (131)I-MAb appears to be valuable as a single agent or when used in combination with other modalities. Results of treating leukaemia and carcinoma cases suggest that re-seeding into the CSF compartment from active systemic disease may account for early relapse in the CNS. One carcinoma case with no apparent systemic disease made a remarkable response and survival for 4 years following a single treatment. Neoplastic meningitis generally carries a dismal prognosis. The results obtained in this initial trial are sufficiently encouraging to stimulate further attempts at CSF therapy with (131)I-MAbs.

This paper reviews the diagnostic role of monoclonal antibody immunohistochemistry in a series of 189 brain tumour biopsies and 22 cases of neoplastic meningitis. The diagnostic monoclonal antibody panel, which includes markers for glial, neural, epithelial and lymphoid differentiation antigens, was used to test a wide variety of cerebral and spinal tumours by indirect immunofluorescence and immunoperoxidase techniques on unfixed frozen sections. Gliomas, meningiomas, schwannomas, medulloblastomas, choroid plexus tumours, cerebral lymphomas and metastatic carcinomas could all be reliably differentiated by means of their characterisctic antigenics profiles, as defined by their patterns of reactivity with the antibody panel. Confident diagnosis was possible even in very poorly differentiated tumours and in biopsies distorted by surgical squeeze artefact, where paucity of morphological clues made diagnosis by conventional histological methods difficult or impossible. It was estimated that use of the antibody panel was responsible for, or made a significant contribution towards the final diagnosis in approximately 20% of cases. The monoclonal reagents were also found to be of great value in the detection and characterisation of neoplastic cells in CSF specimens from patients with malignant meningitis. Malignant cells were detected in 73% of cases and characterised in 16% of cases by routine cytological techniques. Employing monoclonal immunocytology however, these figures were improved to 95% and 95% respectively. Our findings suggest that patients with neoplastic meningtitis can be spared prolonged investigation and inappropriate management by the early detection and characterisation of malignant cells in CSF using panels of monoclonal antibodies.