title: Neurological complications following alemtuzumab-based reduced-intensity allogeneic transplantation.
abstract: We report the incidence, characteristics and outcome of neurological complications occurring following reduced-intensity conditioning (RIC) in 85 patients who received a related/unrelated donor stem cell transplantation following therapy with alemtuzumab, fludarabine and melphalan. Six patients (probability 8.9%) developed severe neurological complications at a median of 151 days (24-334 days). Five of them presented with progressive peripheral sensori-motor radiculo-neuropathy and/or myelitis, preceded by one or more viral reactivation/infection. Despite treatment with immunoglobulins/plasmapheresis/steroids, four died of respiratory failure due to progressive peripheral neurophathy. Viral infection was identified as the only risk factor for the development of neurological complications. Patients who are treated with alemtuzumab-based RIC may have a lower risk of developing regimen-related neurological complications, but are more susceptible to develop peripheral radiculo-neuropathy or myelitis. This phenomenon may be possibly related to viral infection associated with delayed immunological recovery or immunological dysregulation caused by alemtuzumab-induced T-cell depletion.
authors.affiliation: Department of Haematology, University College London, Birmingham Heartlands Hospital, Birmingham, UK. I_avivi@rambam.health.govil
authors.forename: I
authors.initials: I
authors.lastname: Avivi
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: P
authors.initials: P
authors.lastname: Kottaridis
authors.forename: C
authors.initials: C
authors.lastname: Kyriaku
authors.forename: A
authors.initials: A
authors.lastname: Dogan
authors.forename: D W
authors.initials: DW
authors.lastname: Milligan
authors.forename: D
authors.initials: D
authors.lastname: Linch
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: S
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D015994:Incidence; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000821:virology; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014777:Virus Diseases / Q000139:chemically induced / Q000150:complications
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan