title: Successful treatment of childhood pilocytic astrocytomas metastatic to the leptomeninges with high-dose cyclophosphamide.
abstract: Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical benefit. The patients were aged 2.5 to 8 years. Three patients presented with PA localized in the posterior fossa, initially treated with surgical resection (n = 3) and radiotherapy (n = 1). Leptomeningeal dissemination occurred at 32, 44, and 8 months from diagnosis, respectively. The fourth patient presented with an optic pathway tumor with leptomeningeal dissemination at diagnosis. At commencement of cyclophosphamide therapy, disease was present in the subarachnoid space (intracranial, n = 2; spinal, n = 4), cerebral ventricles (n = 2), and primary site (n = 3). Histology was identical at diagnosis and recurrence in the two biopsied cases and cerebrospinal fluid was negative in all cases. Treatment was with cyclophosphamide 4-5 g/m2/cycle given every 4 weeks for a total of two cycles (n = 1) and four cycles (n = 3). One patient achieved disease stabilization (duration 27 months at the time of publication) and three patients experienced significant reductions in tumor burden. Subsequent intrathecal therapy was administered to two patients. Two patients developed disease progression at 10 and 9 months from cessation of chemotherapy. The one re-treated patient responded to further, lower dose, cyclophosphamide. This is the first report of the use of high dose cyclophosphamide for disseminated PA. The recurrence of disease in two cases with a further response to lower dose cyclophosphamide has implications for the optimal duration of therapy for these low grade, aggressive tumors.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: G
authors.initials: G
authors.lastname: McCowage
authors.forename: R
authors.initials: R
authors.lastname: Tien
authors.forename: R
authors.initials: R
authors.lastname: McLendon
authors.forename: G
authors.initials: G
authors.lastname: Felsberg
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: M L
authors.initials: ML
authors.lastname: Graham
authors.forename: J
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: A
authors.initials: A
authors.lastname: Moghrabi
authors.forename: L
authors.initials: L
authors.lastname: Ferrell
authors.forename: T
authors.initials: T
authors.lastname: Kerby
authors.forename: M
authors.initials: M
authors.lastname: Duncan-Brown
authors.forename: E
authors.initials: E
authors.lastname: Stewart
authors.forename: P L
authors.initials: PL
authors.lastname: Robertson
authors.forename: O M
authors.initials: OM
authors.lastname: Colvin
authors.forename: B
authors.initials: B
authors.lastname: Golembe
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003388:Cranial Fossa, Posterior; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000556:secondary*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide