title: Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.
abstract: The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.
authors.affiliation: Istituto Nazionale Neurologico C. Besta, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Salmaggi
authors.forename: A
authors.initials: A
authors.lastname: Dufour
authors.forename: A
authors.initials: A
authors.lastname: Silvani
authors.forename: E
authors.initials: E
authors.lastname: Ciusani
authors.forename: A
authors.initials: A
authors.lastname: Nespolo
authors.forename: A
authors.initials: A
authors.lastname: Boiardi
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology*; D004358:Drug Therapy; D005260:Female; D005909:Glioblastoma / Q000134:cerebrospinal fluid* / Q000473:pathology*; D006801:Humans; D007278:Injections, Spinal; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008527:Medulloblastoma / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy; D013788:Thalamus / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha