title: Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature.
abstract: Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T-cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re-induced with nelarabine 1500 mg/m(2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid-thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced-intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy.
authors.affiliation: Department of Pharmacy, Stanford Hospital and Clinics, Stanford, CA, USA.
authors.forename: Dat
authors.initials: D
authors.lastname: Ngo
authors.affiliation: Department of Pharmacy, Stanford Hospital and Clinics, Stanford, CA, USA SaPatel@stanfordmed.org.
authors.forename: Samit
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Pharmacy, Stanford Hospital and Clinics, Stanford, CA, USA.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: School of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.
authors.forename: Rondeep
authors.initials: R
authors.lastname: Brar
authors.affiliation: School of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Koontz
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D020258:Neurotoxicity Syndromes / Q000175:diagnosis*; D015275:Tumor Lysis Syndrome / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D001087:Arabinonucleosides; C104457:nelarabine
keywords: Neurotoxicity; intrathecal; nelarabine